Genetic Assay to Determine Prognosis in Polycythemia Vera Patients

ABSTRACT

The presently disclosed subject matter provides a genetic assay to determine the prognosis in Polycythemia Vera (PV) patients with an indolent form of PV. This assay involves measuring certain messenger RNAs (mRNAs) in blood cells, such as white blood cells. In some embodiments, the cells are CD34+ cells. These mRNA levels are inserted into an algorithm that yields a predictive score of the risk of PV in the patient transforming from an indolent form to an aggressive form.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 61/724,707, filed Nov. 9, 2012, which is incorporated herein by reference in its entirety.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with United States government support under P01CA108671 awarded by the National Institutes of Health (NIH) and W81XWH-05-1-0347 awarded by the Department of Defense (DOD). The U.S. government has certain rights in the invention.

BACKGROUND

Polycythemia vera (PV) is a hematopoietic stem cell disorder characterized by the increased production of red cells, white cells and platelets and complicated by thrombotic and hemorrhagic events, extramedullary hematopoiesis, and transformation to myelofibrosis or acute leukemia (AML), albeit at variable frequencies (FIG. 1) (Spivak, 2002), and many of these clinical features are shared in common with its companion myeloproliferative disorder, primary myelofibrosis (PMF). PV is unique since with phlebotomy alone its natural history can be measured in decades. However, not all PV patients enjoy substantial longevity or freedom from significant complications but, in contrast to PMF, no satisfactory clinical criteria exist for stratification with respect to the risk of disease transformation, and usually no cytogenetic or molecular markers predictive of disease transformation are present before the event (Gaidano et al., 1997). Although JAK2 V617F is expressed in both PV and PMF, these are stem cell disorders and hematopoietic stem cells are not dependent on this tyrosine kinase for either survival or proliferation (Spivak, 2010), nor has the extent of JAK2 V617F expression been useful for prognostic purposes (Barbui et al., 2011). Bone marrow transplantation is the only curative therapy for PV (Kerbauy et al., 2007) and pegylated interferon is the only drug that can induce a molecular remission, although not in all patients (Kiladjian et al., 2008). Both have significant toxicities, while all chemotherapeutic drugs employed to suppress marrow and extramedullary hematopoiesis as supportive therapy can increase the rate of leukemic transformation ten-fold (Najean and Rain, 1997; Berk et al., 1981).

For many malignancies, gene expression profiling (GEP) has been a useful approach for risk stratifying cancer patients with a shared clinical or histologic phenotype (Radich et al., 2006), and for developing predictors of disease behavior irrespective of the clinical phenotype (Lenz et al., 2008).

SUMMARY

The presently disclosed subject matter provides a genetic assay and kits to determine the prognosis in Polycythemia Vera (PV) patients with an indolent form of PV. The presently disclosed assay involves measuring certain messenger RNAs (mRNAs) in blood cells. These mRNA levels are inserted into an algorithm that yields a predictive score of the risk of PV in the patient transforming from an indolent form to an aggressive form.

In one aspect, the presently disclosed subject matter provides a method for determining the likelihood of an indolent form of Polycythemia Vera (PV) transforming to an aggressive form of PV in a subject, the method comprising: (a) measuring the gene products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 in a biological sample comprising blood cells obtained from the subject; (b) making the following comparisons of the gene product levels measured in (a) and recording a score of 1 for a true result and a score of 0 for a false result: PCNA>IFI30; TSN>CTSA; SMC4>CDKN1A; PCNA>CTTN; SON>CTTN; TIA1>MYL9; (c) adding the scores together to obtain an added score and calculating a ratio of the added score/6 to calculate a total score; and (d) using the total score to predict if the indolent form of PV in the subject is likely to transform to an aggressive form of PV in the subject. In some embodiments, the blood cells are white blood cells. In other embodiments, the blood cells are CD34+ cells.

Accordingly, in some aspects, a total score of 5/6 or 6/6 predicts that the indolent form of PV in a subject is likely to transform to an aggressive form of PV in a subject. In other aspects, a total score of less than 5/6 predicts that the indolent form of PV in a subject is not likely to transform to an aggressive form of PV in the subject.

In another aspect, the presently disclosed subject matter provides a diagnostic kit for determining whether an indolent form of PV in a subject is likely to transform to an aggressive form of PV, the kit comprising a means for measuring the gene product levels of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 and a set of instructions comprising an algorithm for predicting if the indolent form of PV in the subject is likely to transform to an aggressive form of PV.

Certain aspects of the presently disclosed subject matter having been stated hereinabove, which are addressed in whole or in part by the presently disclosed subject matter, other aspects will become evident as the description proceeds when taken in connection with the accompanying Examples and Figures as best described herein below.

BRIEF DESCRIPTION OF THE FIGURES

Having thus described the presently disclosed subject matter in general terms, reference will now be made to the accompanying Figures, which are not necessarily drawn to scale, and wherein:

FIG. 1 shows the natural history of PV as shown by the evolution of PV over time with transformation to myelofibrosis and acute leukemia in 273 PV patients;

FIG. 2 shows quantitative real-time polymerase chain reaction (Q-RT-PCR) confirmation of PV CD34+ cell gene expression using the primers described in Table 1;

FIGS. 3A-3B show representative KEGG pathway analysis for: A) male and B) female patient groups;

FIG. 4 shows a representative Venn diagram of the genes differentially expressed by the 8 men and 11 women PV patients illustrating the number of genes concordantly differentially regulated by both sexes;

FIG. 5 shows a representative dendrogram and heat map for the unsupervised hierarchical clustering of the 19 PV patients using the 102 genes concordantly deregulated by both sexes. The green color bar indicates the normal controls; the blue and red color bars indicate the PV patients. For the heat map, red indicates decreased gene expression and green increased gene expression;

FIG. 6 shows a representative dendrogram and heat map for the supervised clustering of the 19 PV patients using 30 genes identified by top scoring pair analysis. The blue color bar indicates the 12 PV patients with indolent disease and the red color bar the 7 PV patients with aggressive disease. For the heat map, red indicates decreased gene expression and green increased gene expression;

FIG. 7 shows a representative dendrogram and heat map for supervised clustering of the 19 PV patients in blue and the normal controls in red using 21 genes identified by top scoring pair analysis from the 102 core gene set; with the 21 genes the PV patients could be separated almost completely from the normal controls. For the heat map, red indicates decreased gene expression and green increased gene expression;

FIG. 8 shows a representative dendrogram and heat map for the unsupervised hierarchical clustering of the 19 PV patients using the 16 gene “stromal signature.” The blue color bar indicates the indolent patient group and the red color bar aggressive patient group. For the heat map, red indicates decreased gene expression and green increased gene expression;

FIGS. 9A-9B show a representative KEGG pathway analysis for: A) indolent and B) aggressive patient groups;

FIG. 10 shows a representative test using standards for copy number calculations (absolute quantitation). Standard curves were based on log dilutions (10⁶−10¹) of plasmids containing targeted regions of known length of each gene. Copy numbers were determined using calculations based upon the assumption that the average weight of a base pair (bp) is 650 Daltons (g/mol). By utilizing Avogadro's number and converting grams to nanograms, the number of copies of plasmid per weight in ng was calculated by the equation: number of copies=(amount*6.022×10²³)/(length*1×10⁹*650);

FIGS. 11A-11B show: A) ROC curve for the probability score assay using the test set and B) regression and correlation for the probability and clinical scores for the 30 PV patient test set; and

FIGS. 12A-12B show: A) serial probability scores over time in 5 PV patients, with none changing from an indolent to aggressive score; and B) serial probability scores over time in 2 PV patients with an indolent score, with progression to an aggressive score over time in association with leukocytosis and increasing splenomegaly in one, and transformation to acute leukemia in the other without any other clinical change.

DETAILED DESCRIPTION

The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Figures, in which some, but not all embodiments of the presently disclosed subject matter are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated Figures. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

I. PREDICTIVE METHODS FOR PV TRANSFORMATION

PV is complicated by extramedullary hematopoiesis, myelofibrosis and acute leukemia. An explanation for this clinical phenotype was provided by the discovery of an activating mutation (V617F) in JAK2 (James et al., 2005), a tyrosine kinase utilized for signal transduction by the receptors for erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and thrombopoietin. However, the same mutation occurs in essential thrombocytosis (ET) and primary myelofibrosis (PMF), diseases with overlapping phenotypes but distinctly different natural histories (Jones et al., 2005). While it is undisputed that JAK2 V617F can produce a myeloproliferative phenotype, how this mutation could be responsible for the pathogenesis of three different diseases is a conundrum not explainable by the JAK2 V617F allele burden since it overlaps substantially amongst them (Stein et al., 2010). Several lines of evidence suggest that additional genetic and epigenetic events are involved. For example, in PV and ET, gene expression in CD34+ marrow cells was not different in JAK2 V617F-positive and JAK2 V617F-negative patients (Berkofsky-Fessler et al., 2010; Catani et al., 2009), while PV clonal granulocytes do not always express JAK2 V617F (Nussenzveig et al., 2007). Furthermore, JAK2 V617F expression, regardless of its allelic burden, did not influence signal transduction in circulating PV CD34+ cells (Anand et al., 2011). Finally, PV is more common in women (Stein et al., 2010; Ridell et al., 2000) in whom it presents earlier (Ranjan et al., 2013), more often with splenomegaly (Videbaek, 1950), masked erythrocytosis (Lamy et al., 1997), hepatic vein thrombosis (Stein et al., 2011; Smalberg et al., 2012) and a lower JAK2 V617F neutrophil allele burden than men (Stein et al., 2010).

None of the observations should be surprising since myeloproliferative disorders (MPD) are hematopoietic stem cell disorders and animal studies indicate that, unlike committed erythroid and megakaryocytic progenitor cells, primitive hematopoietic stem cells do not require JAK2 or its primary substrate, STAT5, for either survival or self renewal. Further, clonal dominance is a characteristic feature of the MPD, but expansion of the involved JAK2 V617 CD34+ cell population occurs more slowly than that of committed hematopoietic progenitor cell populations, at a different rate in each of the MPD, and independently of JAK2 V617F homozygosity. Importantly in this regard, clonal dominance at the CD34+ cell level correlated better with splenomegaly, leukocytosis and anemia than did the neutrophil JAK2 V17F allele burden and was disease-specific. Finally, gene expression studies of JAK2 V617F-positive PV CD34+ marrow cells indicated dysregulation of JAK2-independent genes, while in ET, gene expression in CD34+ marrow cells did not differ between JAK2 V617F-positive and JAK2 V617F-negative ET patients.

Accordingly, to further define the molecular abnormalities in PV at the stem cell level, gene expression in circulating CD34+ cells from nineteen JAK2 V617F-positive PV patients controlling for gender as a possible confounder was examined. It was observed that CD34+ cell gene expression not only differed between the PV patients and the controls, but also differed between men and women patients. Based on these differences, 102 genes were identified that concordantly differentially regulated by both men and women, which likely represent a core set of genes involved in the pathogenesis of PV.

Using this gene set and several clustering algorithms, the nineteen patients could be separated into two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy, chemotherapy exposure, leukemic transformation and survival. One group had a more aggressive disease with a lower hemoglobin level, more thromboembolic events, larger spleens, a greater frequency of chemotherapy and splenectomy and a higher mortality rate despite having a JAK2 V617F allelic burden similar to the other group. Using a supervised approach, a 19 gene profile was defined, which also segregated the PV patients with aggressive disease from those with a more indolent phenotype with 100% accuracy.

Based on these 19 genes, a smaller gene panel was derived consisting of the 10 genes (PCNA, IF130, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1 and MYL9) for establishing the probability that a PV patient has an aggressive or indolent form of the disease using Q-RT-PCR and scoring 1 for true and 0 for false. If PCNA>IF30; TSN>CTSA; SMC4>CDKN1A; PCNA>CTTN; SON>CTTN; and TIA1>MYL9, the probability that the disease is aggressive is the total score/6. After developing absolute copy number standard Ct curves for the 10 genes, the behavior of this screen on the training set PV patients was verified.

Further, the predictability of the screen was tested using CD34+ cell RNA from twenty-three PV patients. The presently disclosed subject matter provides a molecular method for risk stratification in PV that reflects clinical phenotype and anticipates disease transformation with a high degree of certainty. The data herein indicate that it is now possible to use gene expression to identify those PV patients most likely to benefit from early institution of definitive therapy.

Accordingly, in some embodiments, the presently disclosed subject matter provides a method for determining the likelihood of an indolent form of Polycythemia Vera (PV) transforming to an aggressive form of PV in a subject, the method comprising: (a) measuring the gene products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 in a biological sample comprising blood cells obtained from the subject; (b) making the following comparisons of the gene product levels measured in (a) and recording a score of 1 for a true result and a score of 0 for a false result: PCNA>IFI30; TSN>CTSA; SMC4>CDKN1A; PCNA>CTTN; SON>CTTN; TIA1>MYL9; (c) adding the scores together to obtain an added score and calculating a ratio of the added score/6 to calculate a total score; and (d) using the total score to predict if the indolent form of PV in the subject is likely to transform to an aggressive form of PV in the subject.

In such embodiments, a total score of 5/6 or 6/6 predicts that the indolent form of PV in a subject is likely to transform to an aggressive form of PV in the subject. A total score of less than 5/6 predicts that the indolent form of PV in a subject is not likely to transform to an aggressive form of PV in the subject.

The presently disclosed subject matter provides a 10 gene screening panel comprised of PCNA (proliferating cell nuclear antigen), TSN (translin), CDKN1A (cyclin-dependent kinase inhibitor 1A (p21, Cip1)), MYL9 (myosin, light chain 9, regulatory), IFI30 (interferon, gamma-inducible protein 30), CTSA (cathepsin A), SMC4 (structural maintenance of chromosomes 4), CTTN (cortactin), SON (SON DNA binding protein), and TIA1 (TIA1 cytotoxic granule-associated RNA binding protein).

The biomarkers of the presently disclosed subject matter can be used in diagnostic tests to assess or determine whether an indolent form of PV in a patient will transform to an aggressive form of PV. In other embodiments, the biomarkers may be used to determine if a patient has PV.

The indolent form of PV is characterized by the unregulated production of red cells, white cells and platelets. PV patients afflicted with the indolent form of PV may be asymptomatic or may show milder symptoms of the disease. In contrast, patients with the aggressive form show more severe symptoms, such as thrombotic and hemorrhagic events, extramedullary hematopoiesis, myelofibrosis and acute leukemia, albeit at varying frequencies.

The blood cells can be obtained from different sources in a subject. In some embodiments, the biological sample comprises peripheral blood or bone marrow. In some embodiments, the blood cells are white blood cells. In other embodiments, the blood cells are CD34+ cells.

In some embodiments, the subject is mammalian. In other embodiments, the subject is human.

In further embodiments, the expression products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 are measured. In other embodiments, one or more of these expression products are substituted with other expression products that have both correlated expression and the same category of biological function.

In some embodiments, the expression products of the relevant genes are measured by determining RNA levels. In further embodiments, the expression products are measured by determining mRNA expression levels. Generally, in a first step, the total RNA is isolated from a biological sample. The methods for RNA extraction are well known in the art.

Methods for measuring mRNA levels include methods based on hybridization analysis of polynucleotides as well as methods based on sequencing of polynucleotides. These methods include, but are not limited to, northern blotting, in situ hybridization, RNase protection assays, reverse transcription polymerase chain reaction (RT-PCR), real-time PCR (QPCR), antibodies that can recognize specific duplexes (DNA duplexes, RNA duplexes, DNA-RNA hybrid duplexes, DNA-protein duplexes, for example), sequence-based gene expression analysis including Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS).

In some embodiments, the mRNA expression levels are measured by using reverse transcription PCR (RT-PCR). Commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers. The RT-PCR reaction reverse transcribes the RNA template into cDNA.

In still further embodiments, the mRNA expression levels are measured by using reverse transcription PCR (RT-PCR) followed by real-time PCR (Q-PCR). In the Q-PCR reaction, the cDNA produced from the RT-PCR is amplified and simultaneously quantified. The PCR step can use a variety of thermostable DNA-dependent DNA polymerases, such as Taq DNA polymerase, which has a 5′-3′ nuclease activity but lacks a 3′-5′ proofreading endonuclease activity. Two oligonucleotide primers are used to generate a PCR product. A third oligonucleotide, or probe, is designed to detect the PCR product.

Generally, primer design or determining which sequences to use for making a primer is well known in the art. Computer programs are available to determine if a set of nucleotides in a polynucleotide is optimal for initiating a PCR reaction. Therefore, different primers can be used to initiate a PCR reaction and to detect a specific gene product. As such, the expression products of the presently disclosed subject matter can be detected using different primers and the presently disclosed subject matter is not limited to a specific set of primers.

In other embodiments, the expression products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 are measured by determining protein expression levels. Examples of detection methods for proteins include, but are not limited to, immunohistochemical assays, Western blot analyses, ELISAs, polyacrylamide gels, and protein activity assays. Other detection methods are well known in the art and include methods that are not and need not be stated here.

In some embodiments, the expression products are expression products of variants or fragments of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, or MYL9. Therefore, a gene or gene product comprising variants of polynucleotides according to the presently disclosed subject matter include, but are not limited to, nucleotide sequences which are at least 70% identical, e.g., at least 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleotide sequence of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, or MYL9 may be substituted for PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, or MYL9. In other embodiments, more than one gene may be substituted.

The biological samples used to obtain the RNA of the relevant genes can be any part of a subject that comprises blood cells. In some embodiments, the biological sample comprises peripheral blood or bone marrow. In other embodiments, the biological sample comprises blood cells that are white blood cells. In still other embodiments, the biological sample is comprised of unpurified white blood cells. In further embodiments, the biological sample is comprised of CD34+ cells isolated from unpurified circulating white blood cells. In still further embodiments, circulating CD34+ cells are quantitated clinically by flow cytometry in a pretest step.

In some embodiments, the RNA from a subject is not purified before being used in the presently disclosed methods. In other embodiments, total RNA, such as from unseparated peripheral blood mononuclear cells or from isolated neutrophils, is used in the presently disclosed assays without being purified. In the former case, with respect to the issue of sample dilution and assay sensitivity, the rate limiting step would still be the number of circulating CD34+ cells.

The indolent form of PV in a subject is characterized by many symptoms, both general and specific for the disease. A particular subject may have one or more than one of the symptoms. In some embodiments, the indolent form of PV is characterized by at least one of symptom selected from the group consisting of increased production of red cells, increased production of white cells, increased production of platelets, itching, gouty arthritis peptic ulcer disease, enlarged liver or spleen, elevated hemoglobin levels, and low erythropoietin levels in a subject.

The aggressive form of PV in a subject is generally characterized by more serious symptoms, some of which are life threatening. In some embodiments, the aggressive form of PV is characterized by at least one symptom selected from the group consisting of thrombosis, heart attack, stroke, Budd-Chiari syndrome, myelofibrosis and acute leukemia (AML) in a subject.

PV is chronic disorder, which has a very variable clinical course depending on the host response to the malignant clone (Spivak, 2002). In many patients, the disease remains indolent with only a requirement for phlebotomy therapy to control red cell mass expansion and prevent thrombotic events. In other patients, there is inexorable expansion of the malignant clone with massive splenomegaly for which the treatment options include bone marrow transplantation, interferon or potentially leukemogenic chemotherapy, of which the latter is at best palliative and may actually shorten survival (Berk et al., 1981; Gruppo, 1995). To date, there is no way to anticipate how the disease will evolve clinically. However, the presently disclosed methods can anticipate disease transformation and, based on this, are useful for determining which PV patients would most benefit from the institution of definitive therapy, such as interferon or bone marrow transplantation before clonal expansion is too far advanced. Currently the only curative therapy for PV is bone marrow transplantation and the only therapy capable of inducing molecular remission is pegylated interferon, both of which have significant toxicities. All chemotherapeutic drugs used to suppress marrow and extramedullary hematopoiesis increase the basal rate of leukemic transformation ten-fold or greater. For example, despite the lack of evidence-based data (Spivak, 2002; Spivak and Hasselbalch, 2011), hydroxyurea is considered to be the first-line drug of choice for PV management, particularly in patients older than 65 years of age (Barbui et al., 2011). Unfortunately, hydroxyurea is leukemogenic (Najean and Rain, 1997; Kiladjian et al., 2011) and both age over 60 (McNally et al., 1997) and PV predispose to acute leukemia (Berk et al., 1981), creating a triply dangerous situation for older PV patients since, in contrast to sickle cell disease, a nonclonal disorder in which hydroxyurea improves survival, hydroxyurea neither prevents major vessel arterial or venous thrombosis (Harrison et al., 2005) nor improves survival in PV (Najean and Rain, 1997). Therefore, the presently disclosed methods, which identify PV patients with nonaggressive disease can improve patient safety as well as reduce drug costs. In this regard, the presently disclosed methods can also be used to screen patients for the appropriate use of ruxolitinib when that drug is approved for therapy in PV. Thus, a method to predict transformation risk is very useful to avoid unnecessary exposure to toxic therapies. In some embodiments, the presently disclosed methods are used more than once with a patient to follow PV in the patient. For example, the assay can be used for the first time as a baseline test and then can be used longitudinally as clinically indicated by a rising leukocyte count or advancing splenomegaly, two signs of potentially aggressive behavior in PV. In other embodiments, the presently disclosed methods display a sensitivity of at least 80% and a specificity of at least 90%. In some embodiments, the method further comprises informing the subject or a treating physician of the likelihood of the indolent form of PV transforming to an aggressive form of PV in the subject. In other embodiments, the method is used to determine if a subject should undergo further therapy for PV. In still other embodiments, the method further comprises treating the patient with further therapy for PV. In further embodiments, the therapy is selected from the group consisting of bone marrow transplantation, pegylated interferon, chemotherapy, and ruxolitinib.

II. KITS FOR PREDICTING PV TRANSFORMATION

The presently disclosed subject matter also relates to kits for determining if the indolent PV in a subject will transform to an aggressive form of PV. In general, a presently disclosed kit contains some or all of the components, reagents, supplies, and the like to practice a method according to the presently disclosed subject matter. In some embodiments, the term “kit” refers to any intended any article of manufacture (e.g., a package or a container) comprising a means for detecting the gene products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 and a set of particular instructions for practicing the methods of the presently disclosed subject matter. In other embodiments, the set of particular instructions includes the algorithm for predicting whether the indolent PV in a subject will transform to aggressive PV. In some embodiments, the kit comprises components that detect the levels of RNA transcripts, such as mRNA transcripts. For example, the kit may comprise the primers necessary to detect the mRNA levels of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9, the enzymes necessary to perform reverse transcription and PCR amplification, such as a polymerase and a reverse transcriptase, deoxynucleotides, and a buffer. In other embodiments, the kit comprises components that detect the protein expression levels of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9. The kit provided may be an ELISA kit comprising antibodies to the biomarkers of the presently disclosed subject matter. In still other embodiments, the kit is a diagnostic kit that determines whether an indolent form of PV in a subject is likely to transform to an aggressive form of PV, the kit comprising a means for measuring the gene product levels of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 and a set of instructions comprising an algorithm for predicting if the indolent form of PV in the subject is likely to transform to an aggressive form of PV.

III. DEFINITIONS

Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs.

As used herein, the term “biomarker” refers to any gene, RNA or protein whose level of expression in a cell or tissue is altered in some way compared to that of a normal or healthy cell or tissue. In some embodiments, the amount of biomarker may be changed. In other embodiments, the biomarker may be differentially modified in some way. Biomarkers of the presently disclosed subject matter are selective for PV.

As used herein, the term “level of expression” of a biomarker refers to the amount of biomarker detected. Levels of biomarker can be detected at the transcriptional level, the translational level, and the post-translational level, for example. “mRNA expression levels” refers to the amount of mRNA detected in a sample and “protein expression levels” refers to the amount of protein detected in a sample.

As used herein, the term “microarray” refers to an ordered arrangement of hybridizable array elements, preferably polynucleotide probes, on a substrate.

As used herein, the term “polynucleotide” generally refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA.

As used herein, the term “oligonucleotide” refers to a relatively short polynucleotide. This includes, without limitation, single-stranded deoxyribonucleotides, single- or double-stranded ribonucleotides, RNA:DNA hybrids and double-stranded DNAs.

As used herein, the term “gene product” refers to biochemical material, such as RNA or protein, resulting from expression of a gene. A measurement of the amount of gene product is sometimes used to infer how active a gene is at a particular time.

The term “percent identity,” as known in the art, is a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, as determined by comparing the sequences. In the art, “identity” also means the degree of sequence relatedness between polypeptide or polynucleotide sequences, as the case may be, as determined by the match between strings of such sequences. “Identity” and “similarity” can be readily calculated by known methods, including but not limited to those described in: Computational Molecular Biology (Lesk, A. M., ed.) Oxford University Press, New York (1988); Biocomputing: Informatics and Genome Projects (Smith, D. W., ed.) Academic Press, New York (1993); Computer Analysis of Sequence Data, Part I (Griffin, A. M., and Griffin, H. G., eds.) Humana Press, New Jersey (1994); Sequence Analysis in Molecular Biology (von Heinje, G., ed.) Academic Press (1987); and Sequence Analysis Primer (Gribskov, M. and Devereux, J., eds.) Stockton Press, New York (1991). Preferred methods to determine identity are designed to give the best match between the sequences tested. Methods to determine identity and similarity are codified in publicly available computer programs. Sequence alignments and percent identity calculations may be performed using the Megalign program of the LASERGENE bioinformatics computing suite (DNASTAR Inc., Madison, Wis.). Multiple alignment of the sequences may be performed using the Clustal method of alignment (Higgins and Sharp (1989) CABIOS. 5:151-153) with the default parameters, including default parameters for pairwise alignments. Useful examples of percent sequence identities include, but are not limited to, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, or any integer percentage from 50% to 100%. These identities can be determined using any of the sequence analysis software described herein.

The term “sequence analysis software” refers to any computer algorithm or software program that is useful for the analysis of nucleotide or amino acid sequences. “Sequence analysis software” may be commercially available or independently developed. Typical sequence analysis software will include but is not limited to the GCG suite of programs (Wisconsin Package Version 9.0, Genetics Computer Group (GCG), Madison, Wis.), BLASTP, BLASTN, BLASTX (Altschul et al. (1990) J. Mol. Biol. 215:403-410, and DNASTAR (DNASTAR, Inc., Madison, Wis.). Within the context of this application it will be understood that where sequence analysis software is used for analysis, that the results of the analysis will be based on the “default values” of the program referenced, unless otherwise specified. As used herein “default values” will mean any set of values or parameters which originally load with the software when first initialized.

The term “primer” denotes a specific oligonucleotide sequence which is complementary to a target nucleotide sequence and used to hybridize to the target nucleotide sequence. A primer serves as an initiation point for nucleotide polymerization catalyzed by DNA polymerase, RNA polymerase, or reverse transcriptase.

The term “probe” denotes a defined nucleic acid segment which can be used to identify a specific polynucleotide sequence present in samples, wherein the nucleic acid segment comprises a nucleotide sequence complementary to the specific polynucleotide sequence to be identified.

The terms “complementary” or “complement thereof” are used herein to refer to the sequences of polynucleotides that are capable of forming Watson & Crick base pairing with another specified polynucleotide throughout the entirety of the complementary region. For the purpose of the presently disclosed subject matter, a first polynucleotide is deemed to be complementary to a second polynucleotide when each base in the first polynucleotide is paired with its complementary base. Complementary bases are, generally, A and T (or A and U), or C and G. “Complement” is used herein as a synonym from “complementary polynucleotide,” “complementary nucleic acid” and “complementary nucleotide sequence”. These terms are applied to pairs of polynucleotides based solely upon their sequences and not any particular set of conditions under which the two polynucleotides would actually bind.

The terms “base paired” and “Watson & Crick base paired” are used interchangeably herein to refer to nucleotides which can be hydrogen bonded to one another by virtue of their sequence identities in a manner like that found in double-helical DNA with thymine or uracil residues linked to adenine residues by two hydrogen bonds and cytosine and guanine residues linked by three hydrogen bonds (See Berg et al. (2011) Biochemistry, 7^(th) revised international ed., ISBN-10:1429276355).

Variants of polynucleotides, as the term is used herein, are polynucleotides that differ from a reference polynucleotide. A variant of a polynucleotide may be a naturally occurring variant such as a naturally occurring allelic variant, or it may be a variant that is not known to occur naturally. Such non-naturally occurring variants of the polynucleotide may be made by mutagenesis techniques, including those applied to polynucleotides, cells or organisms. Generally, differences are limited so that the nucleotide sequences of the reference and the variant are closely similar overall and, in many regions, identical.

A polynucleotide fragment refers to a nucleotide sequence of reduced length relative to the reference nucleic acid and comprising, over the common portion, a nucleotide sequence identical to the reference nucleic acid. Such a nucleic acid fragment according to the presently disclosed subject matter may be, where appropriate, included in a larger polynucleotide of which it is a constituent. Such fragments comprise, or alternatively consist of, oligonucleotides ranging in length from at least 6, 8, 9, 10, 12, 15, 18, 20, 21, 22, 23, 24, 25, 30, 39, 40, 42, 45, 48, 50, 51, 54, 57, 60, 63, 66, 70, 75, 78, 80, 90, 100, 105, 120, 135, 150, 200, 300, 500, 720, 900, 1000 or 1500 consecutive nucleotides of a nucleic acid according to the presently disclosed subject matter.

Such fragments may be “free-standing,” i.e. not part of or fused to other polynucleotides, or they may be comprised within a single larger polynucleotide of which they form a part or region. Indeed, several of these fragments may be present within a single larger polynucleotide.

The term “predictive” or “predictability” is used herein to refer to the likelihood that a patient will respond either favorably or unfavorably to therapy. Therapy includes, but is not limited to, drugs, surgical intervention, chemotherapy, radiation therapy, and bone marrow transplants.

As used herein, the terms “treat,” “treating,” “treatment,” and the like, are meant to decrease, suppress, attenuate, diminish, arrest, the underlying cause of a disease, disorder, or condition, or to stabilize the development or progression of a disease, disorder, condition, and/or symptoms associated therewith. It will be appreciated that, although not precluded, treating a disease, disorder or condition does not require that the disease, disorder, condition or symptoms associated therewith be completely eliminated.

As used herein, the terms “prevent,” “preventing,” “prevention,” “prophylactic treatment” and the like refer to reducing the probability of developing a disease, disorder, or condition in a subject, who does not have, but is at risk of or susceptible to developing a disease, disorder, or condition.

As used herein, the term “diagnosing” refers to the process of attempting to determine or identify a disease or disorder.

As used herein, the term “comparing” refers to making an assessment of how the proportion, level or cellular localization of one or more biomarkers in a sample from a patient relates to the proportion, level or cellular localization of the corresponding one or more biomarkers in a standard or control sample. For example, “comparing” may refer to assessing whether the proportion, level, or cellular localization of one or more biomarkers in a sample from a patient is the same as, more or less than, or different from the proportion, level, or cellular localization of the corresponding one or more biomarkers in standard or control sample. More specifically, the term may refer to assessing whether the proportion, level, or cellular localization of one or more biomarkers in a sample from a patient is the same as, more or less than, different from or otherwise corresponds (or not) to the proportion, level, or cellular localization of predefined biomarker levels that correspond to, for example, a patient having an indolent form of PV that is likely to transform to an aggressive form of PV, not having an indolent form of PV that is likely to transform to an aggressive form of PV, is responding to treatment for PV, is not responding to treatment for PV, is/is not likely to respond to a particular PV treatment, or having/not having another disease or condition. In a specific embodiment, the term “comparing” refers to assessing whether the level of one or more biomarkers of the presently disclosed subject matter in a sample from a patient is the same as, more or less than, different from other otherwise correspond (or not) to levels of the same biomarkers in a control sample (e.g., predefined levels that correlate to uninfected individuals, standard PV levels, and the like).

As used herein, the term “transform” means that the condition that is being transformed changes in some way. For example, the indolent form of PV can change to the aggressive form of PV.

As used herein, the terms “indicates” or “correlates” (or “indicating” or “correlating,” or “indication” or “correlation,” depending on the context) in reference to a parameter, e.g., a modulated proportion, level, or cellular localization in a sample from a patient, may mean that the patient has an indolent form of PV that is likely to transform to an aggressive form of PV. In specific embodiments, the parameter may comprise the level of one or more biomarkers of the presently disclosed subject matter. A particular set or pattern of the amounts of one or more biomarkers may indicate that a patient has an indolent form of PV that is likely to transform to an aggressive form of PV (i.e., an indolent form of PV that is likely to transform to an aggressive form of PV). In other embodiments, a particular set or pattern of the amounts of one or more biomarkers may be correlated to a patient being unaffected (i.e., indicates a patient does not have an indolent form of PV that is likely to transform to an aggressive form of PV). In certain embodiments, “indicating,” or “correlating,” as used according to the presently disclosed subject matter, may be by any linear or non-linear method of quantifying the relationship between levels of biomarkers to a standard, control or comparative value for the assessment of the diagnosis, prediction of PV progression or transformation, assessment of efficacy of clinical treatment, identification of a patient that may respond to a particular treatment regime or pharmaceutical agent, monitoring of the progress of treatment, and in the context of a screening assay, for the identification of an anti-PV therapeutic.

The terms “patient,” “individual,” or “subject” are used interchangeably herein, and refer to a mammal, particularly, a human. A “subject” can include a patient afflicted with or suspected of being afflicted with a condition or disease. The patient may have mild, intermediate or severe disease. The patient may be treatment naive, responding to any form of treatment, or refractory. The patient may be an individual in need of treatment or in need of diagnosis based on particular symptoms or family history. In some cases, the terms may refer to treatment in experimental animals, in veterinary application, and in the development of animal models for disease, including, but not limited to, rodents including mice, rats, and hamsters; and primates. Suitable animal subjects include mammals including, but not limited to, primates, e.g., humans, monkeys, apes, and the like; bovines, e.g., cattle, oxen, and the like; ovines, e.g., sheep and the like; caprines, e.g., goats and the like; porcines, e.g., pigs, hogs, and the like; equines, e.g., horses, donkeys, zebras, and the like; felines, including wild and domestic cats; canines, including dogs; lagomorphs, including rabbits, hares, and the like; and rodents, including mice, rats, and the like. An animal may be a transgenic animal. In some embodiments, the subject is a human including, but not limited to, fetal, neonatal, infant, juvenile, and adult subjects.

As used herein, the term “subject at risk” of getting a disease refers to estimating that a subject will have a disease or disorder in the future based on the subject's current symptoms, family history, lifestyle choices, and the like.

As used herein, the term “disease” refers to any condition, dysfunction or disorder that damages or interferes with the normal function of a cell, tissue, or organ.

The term “training set” refers to a group of patients that is used to develop the assay. The testing set is a different group of patients with the same disease used to validate the assay (i.e. reproduce the results).

The terms “measuring” and “determining” are used interchangeably throughout, and refer to methods which include obtaining a patient sample and/or detecting the level of a biomarker(s) in a sample. In one embodiment, the terms refer to obtaining a patient sample and detecting the level of one or more biomarkers in the sample. In another embodiment, the terms “measuring” and “determining” mean detecting the level of one or more biomarkers in a patient sample. Measuring can be accomplished by methods known in the art and those further described herein. The term “measuring” is also used interchangeably throughout with the term “detecting.”

As used herein, the term “indicative” or “likely” means that the event referred to is probable. For example, if the methods of the presently disclosed subject matter result in a conclusion that the indolent form of PV in a subject is likely to transforming to an aggressive form of PV in the subject, then that means it is probable that the indolent form of PV in the subject will transform to an aggressive form of PV.

The terms “sample,” “patient sample,” “biological sample,” and the like, encompass a variety of sample types obtained from a patient, individual, or subject and can be used in a diagnostic or monitoring assay. The patient sample may be obtained from a healthy subject, a diseased patient or a patient having associated symptoms of PV. Moreover, a sample obtained from a patient can be divided and only a portion may be used for diagnosis. Further, the sample, or a portion thereof, can be stored under conditions to maintain sample for later analysis. The definition specifically encompasses blood and other liquid samples of biological origin (including, but not limited to, peripheral blood, serum, plasma, cerebrospinal fluid, urine, saliva, stool and synovial fluid), solid tissue samples such as a biopsy specimen or tissue cultures or cells derived therefrom and the progeny thereof. In a specific embodiment, a sample comprises a blood sample. In another embodiment, a serum sample is used. The definition also includes samples that have been manipulated in any way after their procurement, such as by centrifugation, filtration, precipitation, dialysis, chromatography, treatment with reagents, washed, or enriched for certain cell populations. The terms further encompass a clinical sample, and also include cells in culture, cell supernatants, tissue samples, organs, and the like. Samples may also comprise fresh-frozen and/or formalin-fixed, paraffin-embedded tissue blocks, such as blocks prepared from clinical or pathological biopsies, prepared for pathological analysis or study by immunohistochemistry.

Various methodologies of the instant invention include a step that involves comparing a value, level, feature, characteristic, property, and the like, to a “suitable control,” referred to interchangeably herein as an “appropriate control” or a “control sample.” A “suitable control,” “appropriate control” or a “control sample” is any control or standard familiar to one of ordinary skill in the art useful for comparison purposes. In one embodiment, a “suitable control” or “appropriate control” is a value, level, feature, characteristic, property, and the like, determined in a cell, organ, or patient, e.g., a control or normal cell, organ, or patient, exhibiting, for example, normal traits. For example, the biomarkers of the presently disclosed subject matter may be assayed for levels in a sample from an unaffected individual (UI) or a normal control individual (NC) (both terms are used interchangeably herein). In another embodiment, a “suitable control” or “appropriate control” is a value, level, feature, characteristic, property, and the like, determined prior to performing a therapy (e.g., a PV treatment) on a patient. In yet another embodiment, a transcription rate, mRNA level, translation rate, protein level, biological activity, cellular characteristic or property, genotype, phenotype, and the like, can be determined prior to, during, or after administering a therapy into a cell, organ, or patient. In a further embodiment, a “suitable control” or “appropriate control” is a predefined value, level, feature, characteristic, property, and the like. A “suitable control” can be a profile or pattern of levels of one or more biomarkers of the presently disclosed subject matter that correlates to the presence of an indolent form of PV that is likely to transform to an aggressive form of PV, to which a patient sample can be compared. The patient sample can also be compared to a negative control, i.e., a profile that correlates to not having an indolent form of PV that is likely to transform to an aggressive form of PV.

Following long-standing patent law convention, the terms “a,” “an,” and “the” refer to “one or more” when used in this application, including the claims. Thus, for example, reference to “a subject” includes a plurality of subjects, unless the context clearly is to the contrary (e.g., a plurality of subjects), and so forth.

Throughout this specification and the claims, the terms “comprise,” “comprises,” and “comprising” are used in a non-exclusive sense, except where the context requires otherwise. Likewise, the term “include” and its grammatical variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.

For the purposes of this specification and appended claims, unless otherwise indicated, all numbers expressing amounts, sizes, dimensions, proportions, shapes, formulations, parameters, percentages, parameters, quantities, characteristics, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term “about” even though the term “about” may not expressly appear with the value, amount or range. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are not and need not be exact, but may be approximate and/or larger or smaller as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art depending on the desired properties sought to be obtained by the presently disclosed subject matter. For example, the term “about,” when referring to a value can be meant to encompass variations of, in some embodiments, ±100% in some embodiments ±50%, in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed methods or employ the disclosed compositions.

Further, the term “about” when used in connection with one or more numbers or numerical ranges, should be understood to refer to all such numbers, including all numbers in a range and modifies that range by extending the boundaries above and below the numerical values set forth. The recitation of numerical ranges by endpoints includes all numbers, e.g., whole integers, including fractions thereof, subsumed within that range (for example, the recitation of 1 to 5 includes 1, 2, 3, 4, and 5, as well as fractions thereof, e.g., 1.5, 2.25, 3.75, 4.1, and the like) and any range within that range.

EXAMPLES

The following Examples have been included to provide guidance to one of ordinary skill in the art for practicing representative embodiments of the presently disclosed subject matter. In light of the present disclosure and the general level of skill in the art, those of skill can appreciate that the following Examples are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter. The synthetic descriptions and specific examples that follow are only intended for the purposes of illustration, and are not to be construed as limiting in any manner to make compounds of the disclosure by other methods.

Example 1 Methods

The study protocol was approved by the Johns Hopkins University Institutional Review Board and written informed consent was obtained from each patient in accordance with the Helsinki Declaration. Patients were undergoing diagnostic or therapeutic phlebotomy. The diagnosis of PV was based on the Polycythemia Vera Study Group criteria (Wasserman, 1971). Patient accrual was solely predicated on obtaining sufficient peripheral blood CD34+ cells for analysis. Clinical data including cell counts, spleen size, history of thromboembolic events, chemotherapy and splenectomy were extracted from patient medical records at study entry and termination. Splenomegaly was considered present if the spleen was palpable on physical examination and is reported as centimeters (cm) below the left costal margin.

Neutrophil isolation and DNA preparation were performed as described previously (Williams et al., 2007). Peripheral blood CD34+ cells from PV patients were isolated from Ficoll Paque-processed buffy coats (G5 Healthcare, St. Louis, Mo.) with a purity of greater than 95% and a viability of 98% using immunomagnetic beads (Miltenyi, Auburn, Calif.) according to the manufacturer's instructions, and frozen at −80° C. in 10% DMSO and 90% FBS until studied.

The CD34+ cells were analyzed for CD34, CD38, CD33, CD41 and glycophorin expression using commercially available fluorescent-labeled antibodies. Fluorescence of at least 10,000 cells was measured on a FACS Caliber and analyzed with Cellquest and Paint-a-gate software (BD Biosciences, San Jose, Calif.). Similar to published reports of the peripheral blood CD34+ cell immunophenotype in normal individuals and MPD patients, CD34+ cells from both sources were greater than 98% CD38-positive and 85% CD33-positive; CD41 was expressed on less than 3% of CD34+ cells from both sources, while glycophorin was not expressed by either CD34+ cell population. Cell cycle analysis by flow cytometry using propidium iodide revealed that 91% of the PV and 90% of the mobilized normal CD34+ cells were in Go/G₁ (data not shown).

JAK2 V617F analysis was performed using an allele-specific, quantitative real-time PCR assay sensitive to 5% of either the wild-type or mutant allele (Stein et al., 2010).

For CD34+ cell isolation and analysis, peripheral blood CD34+ cells from PV patients were isolated from Ficoll Paque (G5 Healthcare, St. Louis, Mo.)-processed buffy coats with a purity of greater than 95% and a viability of 98% using immunomagnetic beads (Miltenyi, Auburn, Calif.) according to the manufacturer's instructions, and frozen at −80° C. in 10% DMSO and 90% fetal bovine serum until studied. As controls, G-CSF mobilized peripheral blood CD34+ cells from three normal men and three normal women were obtained from commercial sources (AllCell Technologies LLC, Chicago, Ill. and StemCell Technologies Inc, Vancouver, BC).

The CD34+ cells were analyzed for CD34, CD38, CD33, CD41 and glycophorin expression using commercially available fluorescent-labeled antibodies (Becton Dickinson, San Jose Calif.). Fluorescence of at least 10,000 cells was measured on a FACS Caliber and analyzed with Cellquest and Paint-a-gate software (BD Biosciences, San Jose, Calif.). Similar to published reports of the peripheral blood CD34+ cell immunophenotype in normal individuals and MPD patients (Barosi et al., 2001; Andreasson et al., 1997), CD34+ cells from both sources were greater than 98% CD38-positive and 85% CD33-positive; CD41 was expressed on less than 3% of CD34+ cells from both sources, while glycophorin was not expressed by either CD34+ cell population. Cell cycle analysis by flow cytometry using propidium iodide revealed that 91% of the PV and 90% of the mobilized normal CD34+ cells were in Go/G₁ (data not shown).

Total CD34+ cell RNA was isolated by the RNeasy technique (Qiagen, Valencia, Calif.) with an added DNAse step according to the manufacturer's instructions. To confirm sample quality, duplex RT-PCR was employed to assess RNA integrity (Sugita et al., 2001), and the Agilent Bioanalyzer Lab on a Chip (Agilent Technologies, Inc., Santa Clara, Calif.) was used to confirm that all samples had an optimal rRNA ratio (1:2, for 18S and 28S, respectively), and clean run patterns before microarray analysis.

For oligonucleotide microarray analysis, total RNA samples were processed using the Affymetrix two-round RNA amplification protocol (Affymetrix, Santa Clara, Calif.). Briefly, 100 ng of starting total RNA were used to synthesize first strand cDNA using oligonucleotide probes with 24 oligo-dT plus T7 promoter as primer (Proligo LLC, Boulder, Colo.), and the SuperScript Choice System (Invitrogen, Carlsbad, Calif.). Following the double stranded cDNA synthesis, the product was purified by Affymetrix sample clean up columns, and unlabeled ribonucleotides were used in a first round of in vitro transcription cRNA amplification (MegaScript, Ambion, Austin, Tex.). The following cycle of cDNA synthesis was started with random primers, and the oligo-dT with T7 promoter was again used as primer at the second strand cDNA synthesis step. The ds cDNA product was again column purified. Subsequently, biotinylated anti-sense cRNA was generated through in vitro transcription using the BioArray RNA High Yield Transcript Labeling kit (ENZO Life Sciences Inc, Plymouth Meeting, Pa.). 15 ug of the biotinylated labeled cRNA was fragmented at 94° C. for 35 min (100 mM Tris-acetate, pH 8.2, 500 mM KOAc, 150 mM MgOAC), and bug of total fragmented cRNA was hybridized to the Affymetrix human genome GeneChip array U133A for 16 hr at 45° C. with constant rotation (60 rpm). The Affymetrix Fluidics Station 450 was then used to wash and stain the chips, remove the non-hybridized target and incubate with a streptavidin-phycoerythrin conjugate to stain the biotinylated cRNA. The staining was amplified using goat IgG as blocking reagent and biotinylated goat streptavidin antibody, followed by a second staining step with a streptavidin-phycoerythrin conjugate.

Fluorescence was detected using the Affymetrix GS3000 GeneArray Scanner and image analysis of each GeneChip was done with the GeneChip Operating System software from Affymetrix (GCOS1.1.1), using the standard default settings. For comparison between different chips, global scaling was used, scaling all probe sets to a user-defined target intensity of 150. To assess the QC of the hybridization, chip image, and comparison between chips, the following parameters were studied: the scaling factor, related to the overall intensity of the chip, to confirm the similar signal intensity and staining throughout the samples; background estimation of nonspecific or cross-hybridization; percentage of transcripts that were considered significantly hybridized to the chip (present) by the algorithm; RNA integrity by measurement of the ratio of 3′ to 5′ regions for the housekeeping gene GAPDH, since its presence in the chip and a ratio close to 1 indicates good integrity of the target sample; spikes (BioB/BioC), to confirm the detection level and sensitivity after hybridization.

To assess quality control between replicates, the percentage of differential calls (up or down regulated) was analyzed between pair-wise comparisons, and scatter plot analyses from the different replicates was also conducted to demonstrate reproducibility amongst the experiments. Consistently, the Pearson's correlation coefficients obtained in these studies were between 0.80 and 0.95 for different comparative analyses, and between 0.97 and 0.99 for all duplicate samples. The differences in gene expression associated with RNA amplification as opposed to the analysis of unamplified RNA were also assessed because of the difficulty in obtaining sufficient CD34+ cell RNA for microarray analysis. The results of this analysis indicated that 72% of the present calls were conserved following amplification.

Using the default algorithms for image analysis provided by Affymetrix, approximately 30%-45% of genes represented in the chips were recorded as present in the RNA samples, indicating good quality data. To achieve gene expression signal intensity estimates with a higher precision and a lower false discovery rate (FDR) in differential gene expression analysis, RMA (Robust Multiarray Analysis) was used to improve the Affymetrix default algorithms. RMA also performs quantile normalization to reduce the obscuring variation between microarrays, which might be introduced during the processes of sample preparation, manufacture, fluorescence labeling, hybridization and scanning. With the expression signals estimated as above, a parametric empirical Bayes statistical modeling method, which uses a hierarchical mixture model to account for differences amongst genes in their average expression levels and measurement fluctuations, was employed for differential gene expression analysis between the PV samples and the normal controls. Based on this method, posterior probabilities were obtained, from which inferences regarding differential expression patterns could be made. Specifically, the standard rule of a posterior probability of >0.5 was taken to assert significance in differential gene expression and minimize the false discovery rate.

For Q-RT-PCR validation of the microarray results, additional CD34+ cell samples were analyzed from a subset of the patients by real-time PCR (Q-RT-PCR) without prior RNA amplification. For the mRNA transcripts, first-strand cDNA synthesis was carried out on RNA extracted from the cells with the TaqMan Reverse Transcription Reagents kit (Applied Biosystems, Carlsbad, Calif.) using the oligo d (T)₁₆ RT primer following the manufacturer's suggested protocol. To quantitate miR-21 expression, CD34+ cell RNA was isolated using the mirVana miRNA Isolation Kit (Applied Biosystems) following the manufacturer's procedure for total RNA isolation. The TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems) was used as directed to generate cDNA. Q-RT-PCR was carried out using the gene expression GEX or microRNA assays (Applied Biosystems) listed in Table 1. Duplicate 20 μl reactions were set up using the TaqMan® Universal PCR Master Mix, No AmpErase® UNG (2×), and performed on an Applied Biosystems 7500 sequence detection system using the default “standard 7500” PCR conditions (95° C. for 10 minutes followed by 40 cycles of 95° C. for 15 seconds and 60° C. for 1 minute). For each GEX primer/probe set, a standard curve with known relative concentrations of RNA from either a patient or normal control sample was used to calculate reaction efficiency and quantitate the reaction products. GAPDH reactions were run in parallel samples on the same assay plate. All the GEX Q-RT-PCR results were calculated using the “Standard Curve Assay” program of the 7500 SDS system (Applied Biosystems) and normalized to the GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and the data are shown in FIG. 2. For the miR-21 primer/probe set, relative quantitation using the ΔΔC_(T) calculation method was utilized rather than a standard curve. U6 RNA was the reference RNA.

For supervised analysis, EBarrays analysis was performed for male and female patients separately. The 549 probes that showed a posterior probability greater than 0.5 of differential expression between aggressive and indolent phenotypes in both male and female patients were retained for further analysis. Further analysis of these 549 probes included both genders.

Top-scoring pair analysis (Tan et al., 2005) was run on the 549 probes and the top 30 top-scoring pairs (TSPs) were retained. As some genes had duplicate probes, the R limma package was used, an empirical Bayes test was applied to this data (now both genders), and the highest scoring probe for each gene was retained. The list of TSPs was sorted by the average difference between aggressive and indolent phenotype for that TSP and the six best TSPs were retained. The validation cohort was analyzed using Q-RT-PCR with probes designed to the genes in the retained TSPs. ROC analysis was performed. The AUC for all cases was 0.94, while the AUC excluding AML cases was 0.925. The best point for calls in both cases was setting the call of aggressive phenotype at 5 positive TSP calls, with sensitivity of 0.9 and 0.875 and specificity of 1.0 and 1.0, respectively. The PPV at this threshold was 1.0 in both cases, and the NPV was 0.95 in both cases. A similar approach was used for the supervised analysis of the 19 PV patients and the 6 normal controls.

Gene annotations were developed by collating data from the following data bases: OMIM, Gene, KEGG, AceView, GO Ontology and IPA (Ingenuity Systems, Redwood City, Calif.). The microarray data were deposited in the Gene Expression Omnibus MIAME compliant database (Series number GSE47018) (Edgar et al., 2002).

Example 2 Characteristics of Patients

The clinical features of the 19 patients are listed in Tables 2 and 3. Median age and disease duration were not different between the men and women. All patients expressed JAK2 V617F and the median neutrophil allele burdens in men (94%) and women (100%) were also similar; in 13, the median CD34+ cell JAK2 V617F allele burden was 82% (range 50-100%, data not shown), indicating clonal dominance at both the progenitor cell and neutrophil levels (Moliterno et al., 2008; Stein et al., 2011). The two groups differed significantly (p=0.016) only with respect to their platelet counts, with men having a lower median platelet count (421,000×10³/μL) than the women (948,000×10³/μL), which may reflect a gender-related difference (Segal and Moliterno, 2006).

Example 3 Gene Expression in Men and Women Patients

Given the differences in disease behavior between men and women PV patients, it was hypothesized that there could be gender-specific differences in gene expression independent of JAK2 V617F expression. Therefore, patient gene expression was compared with controls of the corresponding gender and it was found that there was differential gene expression in women patients compared to men, with 251 genes differentially regulated (126 up and 109 down) in women (Table 4) compared to 535 genes (486 up and 85 down) in the men (Table 5). Despite a smaller number of deregulated genes, KEGG analysis revealed that over three times as many molecular pathways were activated in the women patients, including one, the pentose phosphate pathway, which was not activated in any male patient (FIGS. 3A-3B).

Example 4 Identification of Concordantly Deregulated Genes by the Men and Women Patients

Subtracting genes whose expression was gender-specific left 102 genes (68 up regulated and 34 down regulated), whose differential expression was concordant in both men and women (FIG. 4), and could represent a core set of genes involved in the pathogenesis of PV. Gene expression was validated for 8 of the 102 genes by Q-RT-PCR (Table 1) using CD34+ cells from a subset of the patients, and there was good correlation between the observed microarray gene expression changes and the Q-RT-PCR measurements (FIG. 2).

Example 5 Unsupervised Hierarchical Clustering Using the 102 Concordantly Deregulated Genes

Unsupervised hierarchical clustering was employed to determine if the 102 core gene set segregated the PV patients from the normal controls. As shown in FIG. 5, the PV patients clustered into two distinct groups, one of which clustered independently from the controls and demonstrated heterogeneity with respect to core gene expression, while the other was more homogeneous and overlapped with the controls. Table 6 lists the clinical features of the two patient groups, which did not differ with respect to age, JAK2 V617F neutrophil allele burden, leukocyte and platelet counts or clonal dominance. However, they did differ statistically with respect to disease duration, hemoglobin level, thromboembolic events, palpable splenomegaly, splenectomy, chemotherapy exposure, leukemic transformation and survival, indicating that disease behavior was aggressive in one group and indolent in the other.

To validate the unsupervised hierarchical clustering, a supervised approach based on top-scoring pairs was used (Tan et al., 2005). A 30 gene set was identified, none of which were in the 102 core gene set, which segregated the patients into the same aggressive and indolent clinical groups with 100% accuracy, validating the unsupervised hierarchical clustering results (FIG. 6).

Example 6 Annotation of the 102 Concordantly Deregulated Genes

Annotation of the 102 genes is provided in Table 7. Of note, there was differential regulation of the stem cell maintenance genes HES1, HOXA9, PTGER4 and NR4A2, the master transcription factor SOX4 and the oncogenes SETBP1 and miR-21. Eight antiapoptotic genes, LEPR, CKAP4, RRAS2, TIMP1, IER3, THSB1, POSTN, and LGALS3, were up regulated while five proapoptotic genes, EIF5A, EMP1, ZFP36L2, LUC7L3, HLF and HOPX and three tumor suppressor genes, SSBP2, TLE4 and KLF6 were down regulated.

Importantly, consistent with the propensity for myelofibrosis in PV, there was up regulation of 16 extracellular matrix genes, including six collagen genes (COL1A1, COL1A2, COL3A1, COL4A1, COL4A2 and COL6A3), and the matricellular genes SPARC, POSTN, TIMP1, THBS1, HSPE, FN1, S1OOA9, EFEMP1, LGALS3, and LTBP3, essentially comprising a “stromal gene signature”. Furthermore, given the inflammatory milieu that characterizes the MPD (Slezak et al., 2009; Verstovsek et al., 2010), there was increased expression of 10 cytokine and inflammatory mediator genes, CCL3 (MIP1-α), CCL5 (RANTES), CXCL5, SERPINE1 (PAI-1), S100A9, LCN2, PTX3, PF4V1, FCN1 and CFD, similarly comprising a “cytokine gene signature”.

Given the striking dysregulation of extracellular matrix protein genes, unsupervised hierarchical clustering was used to determine whether stromal gene expression segregated with a particular clinical phenotype. As shown in FIG. 8, the stromal gene set also separated the aggressive and indolent groups, with the latter showing the same heterogeneity seen using the 102 core gene classifier (FIG. 5).

Example 7 Gene Expression in the Aggressive and Indolent Patient Groups

Analysis of differential gene expression in the aggressive and indolent groups reinforced the importance of JAK2 V617F-independent expression of disease phenotype-modifying genes. For example, although there was no difference in the JAK2 V617F allelic burdens between the two groups (Table 6), gene expression differed markedly with 707 genes differently regulated (248 up and 459 down regulated) in the indolent group as compared to the controls (Table 8), while only 149 genes were differentially regulated (68 up and 81 down regulated) in the aggressive group (Table 9). Furthermore, the two groups also differed markedly with respect to expression of the 102 core genes (Tables 10 and 11). KEGG analysis (FIGS. 9A-9B) emphasized the predominance of deregulated molecular pathways involving DNA and RNA metabolism and function in both groups but histone gene deregulation predominated in the aggressive group.

Example 8 Expression of PV Core Genes in the Chronic and Blast Crisis Phases of Chronic Myelogenous Leukemia

Finally, to determine if the gene expression changes in the 102 core genes were unique to PV or a nonspecific consequence of constitutive tyrosine kinase activation, the expression of these genes was examined in the chronic and blast crisis phases of chronic myelogenous leukemia (CML) (Bruns et al., 2009; Diaz-Blanco et al., 2007; Graham et al., 2007; Nowicki et al., 2003; Zheng et al., 2006; Yamamoto-Sugitani et al., 2011; Nakahara et al., 2010), a disease characterized by constitutive tyrosine kinase signaling in which STAT5 phosphorylation has a central role in disease pathogenesis (Horita et al., 2000; Hantschel et al., 2012). As shown in Table 12, there was concordant up regulation of 16 PV core genes in chronic phase CML, with concordant down regulation of 9. This pattern was reversed in CML blast crisis, with up regulation of 6 down regulated PV core genes, including the oncogene SETBP1, and down regulation of 11 up regulated PV core genes. Listed are 55 genes from the 102 core PV gene set showing their regulation in chronic phase and blast phase CML (Bruns et al., 2009; Diaz-Blanco et al., 2007; Graham et al., 2007; Nowicki et al., 2003; Zheng et al., 2006; Yamamoto-Sugitani et al., 2011; Nakahara et al., 2010). White background indicates concordant regulation in P and grey background indicates discordant regulation in PV.

Example 9 Discussion of Gene Expression Profiling in PV

PV has been scrutinized scientifically for decades but its molecular basis remains an enigma. In contrast to CML with its characteristic t(9; 22)(q34; q11) translocation and resulting BCR-ABL fusion tyrosine kinase gene, no genetic defect or protein marker specific for PV has yet been identified despite the use of high resolution techniques such as oligonucleotide array comparative genomic hybridization and high resolution single nucleotide polymorphism array karyotyping.

Central to the success of the strategy disclosed herein was the choice of an informative target cell population, a control cell population matched with respect to origin and phenotype, and avoidance of confounding effects on gene expression. Since PV is a stem cell disorder, CD34+ cells were studied. Because myelofibrosis is part of its natural history, to ensure inclusive patient representation, as well as easy access for the repeated harvests necessary to obtain sufficient cells for analysis, peripheral blood CD34+ cells were chosen rather than their marrow counterparts. At the same time, without being bound to any one particular theory, there is no reason to believe that there would be distinctly different gene expression patterns in blood and marrow CD34+ cells since this has not been the case for either acute myelogenous leukemia or CML.

The approach used herein was facilitated by the characteristic constitutive mobilization of CD34+ cells in PV, which represents an endogenous purification step with respect to residual nonclonal marrow CD34+ cells. Although the presence of circulating nonclonal CD34+ cells is still a potential confounder, clonal dominance is another feature of PV that results in suppression of polyclonal hematopoiesis and serves as an additional endogenous purification step.

As demonstrated by the quantitative JAK2 V617F neutrophil allelic burden in all 19 patients, and in CD34+ cells in thirteen, clonal dominance was present in all patients, reducing or eliminating contamination of patient CD34+ cells by normal CD34+ cells. Additionally, since only 6 patients (26%) were receiving chemotherapy at the time of study and five of these were taking hydroxyurea, which only affects dividing cells, it is unlikely that drug effects were a significant confounder with respect to CD34+ cell gene expression.

G-CSF mobilized peripheral blood CD34+ cells from normal subjects as the control study population were chosen because they have not been found to differ from their steady state peripheral blood counterparts with respect to cell cycle activity, immunophenotype and gene expression, while differing significantly from marrow CD34+ cells with regards to these and gene expression, as well. Both G-CSF mobilized normal CD34+ cells and PV peripheral blood CD34+ cells were similar with respect to immunophenotype and cell cycle activity, with both largely in G₀/G₁ in contrast to marrow CD34+ cells, which are actively cycling. Furthermore, and most importantly, G-CSF exposure was unlikely to be a confounder with respect to CD34+ cell gene expression because these cells do not express G-CSF receptors, PV neutrophils are also already constitutively activated by virtue of JAK2 V617F expression, and plasma G-CSF is also increased in this disorder.

Given the number of CD34+ cells required to obtain sufficient mRNA for analysis, no attempt was made to fractionate patient or control peripheral blood CD34+ cells on the basis of immunophenotype before microarray analysis. This has clinical relevance since the data herein establishes that unfractionated patient peripheral blood CD34+ cells can serve as an informative cell population for analyzing clinical risk assessment at the molecular level.

Because of the differences in disease frequency, disease manifestations, disease complications and JAK2 V617F expression between men and women PV patients, it was hypothesized that gender might also be a confounder with respect to gene expression and analyzed each patient individually with a gender-specific control. As shown in FIG. 4, sex was, indeed, an important confounder; women patients differentially up or down regulated only 251 genes compared to 535 genes for the men. The biological basis for this difference is unknown but it fits with the observed suppression of the myeloproliferative clone during pregnancy, and thus could have an epigenetic, hormonal or immunologic basis.

The importance of these genes in the disease process was substantiated by the fact that they could be used to segregate a disorder perceived to be monolithic into two groups with distinctly different clinical features and complication rates that were independent of sex as well as the JAK2 V617F allelic burden (Table 2). Although the study population was small, the aggressive group fits the clinical phenotype of the 10-15% of PV patients who develop the post-polycythemia myelofibrosis syndrome, and these are the same patients who are at risk of the spontaneous evolution of a JAK2 V617F-positive acute leukemia. In this regard, it is of interest that with gene expression profiling it was possible to identify those CML patients in the chronic phase of the disease who were at risk of early transformation, or who had already transformed at the molecular level despite a chronic phase clinical phenotype.

In contrast to primary myelofibrosis, for which there are well-validated prognostic factors for risk stratification at diagnosis and during disease progression, to date no such prognostic factors have been identified under either circumstance for PV and, as the data herein indicate, neither the JAK2 V617F allelic burden nor clonal dominance per se are useful in this regard. However, the data suggest that differential gene expression could be useful. Since gene expression appeared largely fixed from disease diagnosis for the indolent group, it is possible that acquisition of new genetic lesions in the aggressive group, whether spontaneous or treatment-related was responsible for disease transformation. The latter appeared to be the case in one indolent group patient, who developed therapy-related acute leukemia associated with the acquisition of a 5q-abnormality while taking hydroxyurea. Thus, the presently disclosed 30 gene classifier can be used to identify during the course of the disease, those patients who might benefit from early therapeutic intervention with pegylated interferon or allogeneic stem cell transplantation, while sparing other patients the side effects of unnecessary treatment.

Gene expression was examined in circulating PV CD34+ cells after removing gender as a potential confounder. This led to the identification of 102 genes whose importance in the disease process was substantiated by the fact that they could be used to segregate the PV patients into two groups with distinctly different clinical features independent of the JAK2 V617F allelic burden, leukocyte and platelet counts. The aggressive group fit the phenotype of PV patients who develop the post-polycythemia myelofibrosis syndrome (Silverstein, 1974; Passamonti et al., 2008), and are at risk of spontaneous leukemic transformation (Beer et al., 2009). In this regard, during chronic phase CML, it was possible using gene expression to identify patients who were at risk of early transformation, or who had already transformed at the molecular level (Radich et al., 2006). Thus, given the low frequency of cytogenetic abnormalities in PV before disease transformation (Gangat et al., 2008; Stein et al., 2011), gene expression profiling could have prognostic relevance in PV.

With respect to disease specificity, it was informative to examine the expression of the 102 PV core genes in chronic and blast phase CML CD34+ cells (Bruns et al., 2009; Diaz-Blanco et al., 2007; Graham et al., 2007; Nowicki et al., 2003; Zheng et al., 2006; Yamamoto-Sugitani et al., 2011; Nakahara et al., 2010). Fifty-five of the 102 PV core genes were dysregulated in CML, with concordant dysregulation of 25 in chronic phase CML.

However, with blast crisis, there was a reversal of the up or down regulation of 17 PV core genes, providing a window into the genetic mechanisms that govern the clinical behavior of these two disorders and the potential relevance of specific genes or pathways in maintaining normal differentiation or promoting leukemic transformation. Interestingly, the gene expression profile of the aggressive group, as in CML blast crisis patients, was closest to that of normal CD34+ cells (Radich et al., 2006).

The mechanisms driving differential gene deregulation in PV are unknown but rather than behaving like canaries in a mine shaft, gene expression appeared to be cell autonomous, a contention supported by the comparison with CML CD34+ cell gene expression (Table 12). The extent to which JAK2 V617F contributed to gene expression remains undefined but no significant differences in gene expression were observed in a study of PV CD34+ marrow cells from JAK2 V617F-positive and negative patients (Berkofsky-Fessler). In this study, the JAK2 V617F allelic burdens were not different between the aggressive and indolent groups even though their gene expression patterns differed both globally (Tables 8 and 9), as well as with respect to the 102 core gene set (Tables 10 and 11), supporting an important role for other signaling pathways in PV pathogenesis.

The 102 core gene list provides ample evidence for this contention and for synergistic interactions amongst these pathways as well. For example, HES1 up regulation suggests activation of either the Notch or Hedgehog pathways and couples these pathways with JAK2-STAT3 signaling, and NF-κB and HIF-1α activation (Kamakura et al., 2004; Wall et al., 2009; Lee et al., 2009; Espinosa et al., 2010). LEPR, LGALS3, LTBP3 and THBS1 activate TGF-β1 (Wang et al., 2009; Mackinnon et al., 2012; Koli et al., 2008; Daniel et al., 2004), whose target genes include SOX4, SPARC, SERPINE1 (PAI-1) and miR-21 (Scharer et al., 2009; Shibata and Ishiyama, 2013; Baricos et al., 1999; Patel and Noureddine, 2012). SOX4 is also associated with activation of the Wnt, Notch and Hedgehog pathways (Scharer et al., 2009) and up regulation of HOXA9 (Scharer et al., 2009; Ikushima et al., 2009); which in turn enhances the transcriptional activity of SOX4 and STAT5 (Huang et al., 2012). LGALS3 also enhances Wnt pathway activity (Song et al., 2009); TIMP1 and SOX4 activate the PI3-K/AKT pathway (Scharer et al., 2009; Ridnour et al., 2012), while RRAS2 activates the RAF/MAPK/ERK and PI-3K/AKT pathways (Rosario et al., 2001; Rosario et al., 1999).

Other striking abnormalities were the up regulation of 16 genes encoding important matricellular proteins, essentially comprising a stromal signature similar to that described in lymphomas and breast cancer (Lenz et al., 2008; Bergamaschi et al., 2008), and 10 inflammatory cytokine genes, comprising a cytokine signature. The stromal signature identified genes probably involved in PV myelofibrosis (Tripodo et al., 2012) as well as in CML myelofibrosis (Yamamoto-Sugitani et al., 2011), and confirms the importance of malignant CD34+ cells in marrow stem cell niche maintenance and remodeling (Schepers et al., 2013). The cytokine signature not only adds new members to those previously identified as involved in PV (Slezak et al., 2009; Verstovsek et al., 2010), but also identifies genes linking inflammation with coagulation such as the complement-activating genes, CFD, FCN1 and PTX3. In addition, the data suggest a potential prothrombotic role for PF4V1, SERPINE1 (PAI-1), HSPE and THSB1, which antagonizes both nitric oxide (Isenberg et al., 2005) and ADAMTS13 (Bonnefoy and Hoylaerts, 2008), and the prothrombinase, FGL2 (Yuwaraj et al., 2001), a gene not previously identified as up regulated in PV.

The CD34+ cell population is diverse, and, although for technical reasons the cells could not be further fractionated, the study disclosed herein confirms that analysis of unfractionated circulating CD34+ cells has clinical utility (Radich et al., 2006). Gene expression, of course, only represents one component of the complex process from gene transcription to protein product and is subject to epigenetic as well as genetic influences not controlled for in this study. Nevertheless, the data provide new insights into the molecular abnormalities of PV, establish a molecular basis for disease heterogeneity, identify genes and pathways for targeted therapy outside the canonical JAK2 signaling pathway, as well as previously unrecognized genes potentially involved in promoting myelofibrosis, inflammation and thrombosis.

This study has identified a number of important genes that may be worthy of consideration for targeted therapy. They include HES1, a transcriptional repressor that negatively regulates the tumor suppressor PTEN, SPARC a multifunctional, antiadhesive matricellular protein that regulates extracellular matrix organization and up regulates osteopontin, a protein responsible for stem cell niche maintenance, and LGALS3 and TIMP1, the cognate ligand for CD36, which promotes platelet aggregation, antagonizes nitric oxide and activates TGF-β. In addition to TIMP1, the up regulation of a number of previously recognized coagulation genes that may contribute to the thrombotic diathesis that complicates PV were also identified. These include the fibrinolysis inhibitor PAI-1 and the prothrombinase FGL2, as well as the gene PTX3.

Hematopoietic stem cells do not require JAK2 for either survival or proliferation and no difference was found between the size of the hematopoietic stem cell compartment between PV, ET and normal controls in vivo or their behavior in vitro. This is not surprising since JAK2 expression and activation in a JAK2-naive cell line did not appear to alter global gene transcript above that observed with unactivated JAK2 expression. Furthermore, no significant changes in gene expression were observed in a study of PV CD34+ marrow cells from JAK2 V617F-positive and negative patients, nor was a significant difference observed when the gene expression in PV CD34+ marrow cells was compared with that following overexpression of wild type JAK2 in normal CD34+ cells. Similar observations have been made with CD34+ marrow cells from JAK2 V617F-positive and negative ET patients. At the same time, it is well documented that in the nucleus, JAK2 directly modifies gene transcription and enhances mitotic recombination and promotes genetic instability by altering histone phosphorylation and methylation and damaging DNA by generating reactive oxygen species, which may be its most important contributions to PV stem cell behavior. In addition to the influence of JAK2 V617F, our data indicate activation of a number of other signal transduction pathways. For example, HES1 expression is dependent on either the Notch or Hedgehog pathways and HES1 itself activates STAT3 through either SRC or JAK2 signaling.

A striking abnormality was up regulation of genes encoding matricellular proteins and inflammatory cytokines. Whether such signals are the consequence of constitutive JAK2 activation involving stem cell cytokine receptors is unclear but with respect to the genes whose expression is normally influenced by JAK2, only two genes, SPARC and PTX, the latter a gene normally down regulated by JAK2, were up regulated in the PV CD34+ cells, suggesting that gene expression in these cells was driven by signal pathways primarily unrelated to JAK2. This contention is supported by the upregulation of genes involved in Notch or Hh signaling such as HES1, genes involved in NFK-β signaling such as NR4A2, IER3, and RRAS2, genes involved in Wnt signaling such as LGALS3, GAS2, SPARC and S100A9, and genes involved in TGF-β signaling such as LGALS3, TIMP1, THSB1 and LEPR.

With respect to the specificity of gene expression associated with JAK2 signaling in PV CD34+ cells, it was informative to compare their gene expression profiles with those of chronic phase CML CD34+ cells, since constitutive tyrosine kinase signaling involving STAT5 is a central feature of both disorders and both share a similar clinical phenotype with respect to leukocytosis, thrombocytosis, extramedullary hematopoiesis, myelofibrosis and transformation to acute leukemia, although at differing frequencies, possibly because BCR-ABL signaling is ectopic while signaling by JAK2 V617F occurs through physiologic pathways.

As shown in Table 12, there was concordant dysregulation of 28 of the PV 105 core gene set in chronic phase CML, which is compatible with the observation that STAT5 is activated by BCR-ABL signaling. By contrast, however, in CML blast crisis, there was a reversal in the up or down regulation of 17 PV core set genes, providing a window into the genetic mechanisms that govern the different clinical courses of these two disorders and the potential relevance of specific genes or pathways in maintaining normal differentiation or promoting leukemic transformation. In this regard, it is interesting to note that the gene expression profile of both the aggressive patient group and those CML patients who developed blast crisis was not only different from the indolent group or chronic phase CML patients respectively, but also closer to that of normal CD34+ cells.

This study provides a snap shot of gene expression in a heterogenous stem cell population of a chronic disorder characterized by phenotypic variability over time. The data provide insight into the molecular abnormalities of PV, identify new candidate genes for targeted therapy outside the canonical JAK2 signaling pathway and as well as previously unrecognized genes that may be involved in promoting thrombosis in PV patients.

The molecular behavior of PV CD34+ cells has been exposed in this study. The data indicate that PV can no longer be considered a monolithic disorder with bone marrow failure as an inevitable event, that patients with an aggressive form of the disorder can be identified early in the course of their disease and that, as has been previously argued, women PV patients cannot be treated as small men, and this should be true both in clinical trials and in pregnancy. Whether controlling for sex as a potential confounder is applicable to gene expression analysis in other hematologic malignancies is worthy of evaluation given the remarkable insights described here.

Recent studies have suggested that in PV, as well as in CML, the disease may arise in a later stage progenitor cell, and, in particular, one with a predilection for erythroid differentiation. While the data herein do not directly speak to this contention, in keeping with it, six globin genes were upregulated in PV CD34+ cells. However, it is noteworthy that in chronic phase CML there was up regulation of the α₂, β, δ and γ₂ globin genes as well as an increase in the MEP population despite the fact that CML is phenotypically myeloid-restricted, while PV is not. Therefore, without wishing to be bound to any one particular theory, it is believed that as opposed to being associated with CD34+ maturation status, these gene expression changes may merely reflect nonspecific up regulation of gene expression by JAK2 activation in both disorders, or aberrant activation of multiple genetic pathways in a transformed pluripotent stem cell as can be seen in biphenotypic leukemias. The up regulation of both embryonic and fetal globin genes supports this latter contention, as does the observation that in vivo, the balance between erythroid and myeloid progenitor cell pools in PV was not different from normal.

Example 10 10 Gene Screening Panel for Predicting Aggressive Forms of PV

Since PV is a stem cell disorder, PV CD34+ cells were examined for constructing a gene

screening panel for PV. Specifically, to avoid repeated marrow aspirations to collect these cells, circulating CD34+ cells were studied. This was also technically advantageous because an increase in the number of circulating CD34+ cells is a feature of PV, and because of clonal dominance, which is also a feature of PV, the bulk of the circulating CD34+ cells were likely to be from the malignant clone (Adamson et al., 1976). Mobilized normal circulating CD34+ cells, which are immunophenotypically similar and have the same cell cycle status, were used as the control cell population, and, because female PV patients have different clinical features than male patients (Stein et al., 2010; Stein et al., 2011; Videbaek, 1950), each patient was compared with a gender-specific control. Using oligonucleotide microarray technology, it was found that women differentially regulated 251 genes and men 535 genes, but both concordantly differentially regulated 102 genes (FIG. 4). Using this 102 core gene set and unsupervised hierarchical clustering, PV patients were able to be segregated into two groups (FIG. 5), with one group having a more aggressive disease with lower hemoglobin levels, more thromboembolic events, a higher frequency of splenomegaly, larger spleens, a greater frequency of chemotherapy and splenectomy, more leukemic transformation and a higher mortality rate, despite having a JAK2 V617F allelic burden similar to the other group (Table 6). Using a supervised approach, top scoring pairs, a 29 gene profile was defined, which also segregated the PV patients with aggressive disease from those with a more indolent phenotype with 100% accuracy (FIG. 6).

Based on these 19 genes, a smaller gene panel was derived consisting of 10 genes (PCNA, IF130, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1 and MYL9) for establishing the probability that a PV patient has an aggressive or indolent form of the disease. Using qRT-PCR and scoring 1 for true and 0 for false. If PCNA>IF30; TSN>CTSA; SMC4>CDKN1A; PCNA>CTTN; SON>CTTN; and TIA1>MYL9, the probability that the disease is aggressive is the total score/6. After developing absolute copy number standard curves for the 10 genes (FIG. 10), the behavior of this screen on seven patients was verified in the initial training set and its predictability examined in a blinded fashion using CD34+ cell RNA from 30 additional PV patients as described herein below.

For biomarker association with clinical measures, patient probability scores were correlated with the presence or absence of clinical complications as defined from the training set aggressive PV group and calculated as a clinical score (0-6). These clinical complications were: anemia, palpable splenomegaly or history of splenectomy, spleen size, major vessel thrombosis, chemotherapy or immunomodulatory therapy and leukemic transformation. Of the 30 patients, 8 had clinical features compatible with the aggressive form of PV with a median clinical score of 3.0 (range, 2-4) and a median probability score of 5/6 (range, 5-6) using the 10 gene panel. In these 8 patients, each of the clinical complications occurred at a significantly higher frequency than in the indolent group. Of the 22 patients who did not have an aggressive clinical phenotype, the median clinical score was 1 (range 0-3) and the median probability score was 3/6 (range 0-4) (Table 13). The difference in clinical scores between the two groups was statistically significant (p<0.001), and the probability score was also significantly different between the groups at p<0.001 with a ROC curve with an AUC of 0.94 (FIG. 11A). There was good correlation between the probability score and the clinical score in this group of patients (p=0.002; FIG. 11B). Median disease duration was 15.5 years (range, 9-39) in the aggressive group and 7.0 years (range, 1-27; p=0.011) in the indolent group (p=0.003), while the median JAK2 V617F allelic burden was not different in the aggressive group compared to the indolent group (94% vs 81%), though 5 of the indolent group, but none of the aggressive group, had allele burdens of 50% or less. In 7 patients, it was possible to obtain repeat measurements over a period of 3-5 years and in 5, the probability score remained constant at 4/6 or less with similar JAK2 V617F allelic burdens and clinical scores (FIG. 12A). In one patient with a probability score of 1-2/6, the probability score increased to 5/6 in advance of AML transformation in one (FIG. 12B).

Table 14 discloses the genes and context sequences (probe sequences; Applied Biosystems primer/probe kits) comprising the 10 gene screening panel for the presently disclosed methods. Table 15 shows representative NCBI Accession numbers for each gene and Table 16 discloses the probes (Life Technologies, Carlsbad, Calif.) used to detect each gene.

After cloning the appropriate probes and developing absolute copy number standard Ct curves for the 10 genes, the behavior of this screen on PV patients in the training set was verified. The predictability of this screen was examined using CD34+ cell RNA from a test set of 23 PV patients (Tables 18 and 19). Patient probability scores were correlated with the presence or absence of clinical features defined by the training set aggressive PV group and calculated as a clinical score. Of the 23 patients, 7 had clinical features compatible with the aggressive form of PV with a median clinical score of 3.0 (range, 1-6) and a median probability score of 6/6 (range, 3-6), with one patient having a score of 3/6. Of the 16 patients who did not have an aggressive clinical phenotype, the median clinical score was 0 (range 0-1) and the median probability score was 3/6 (range 1-4). The difference in clinical scores between the two groups was statistically significant (p<0.001) and the probability score was also significantly different between the groups at p=0.001. Median disease duration was 13.0 years (range, 9-39) in the aggressive group and 6.0 years (range, 1-17) in the indolent group (p=0.003), while the median JAK2 V617F allelic burden was greater in the aggressive group (95% vs 82.5%; p=0.04) with 5 of the indolent group, but none of the aggressive group, having allele burdens of 50% or less. In 2 patients, it was possible to obtain repeat measurements over a period of 3-5 years and in both the probability score remained constant at 4/6 with similar Jak2 V617F allelic burdens and clinical scores. In one patient with a probability score of 3/6, the score increased to 6/6 in advance of AML transformation. ROC (Receiver Operating Characteristic) analysis revealed that the AUC for all cases was 0.94, while the AUC excluding AML cases was 0.925. The best point for calls in both cases was setting the call of aggressive phenotype at 5 positive TSP calls, with sensitivity of 0.9 and 0.875 and specificity of 1.0 and 1.0, respectively. The PPV at this threshold was 1.0 in both cases, and the NPV was 0.95 in both cases. (AUC=area under the curve; FN=falsely negative; FP=falsely positive; TP=total positives; TN=total negatives).

The power of a diagnostic test to correctly predict status is commonly measured as the sensitivity of the assay, the specificity of the assay or the area under a receiver operated characteristic (“ROC”) curve. Sensitivity is the percentage of true positives that are predicted by a test to be positive, while specificity is the percentage of true negatives that are predicted by a test to be negative. A ROC curve provides the sensitivity of a test as a function of 1-specificity. The greater the area under the ROC curve, the more powerful the predictive value of the test. Positive predictive value is the percentage of people who test positive that are actually positive. Negative predictive value is the percentage of people who test negative that are actually negative.

Relevant equations are defined below:

Sensitivity=TP/(TP+FN)

Specificity=TN/(TN+FP)

PPV(positive predictive value)=TP/(TP+FP)

NPV(negative predictive value)=TN/(TN+FN)

The positive predictive value is often reported as it gives the probability that a patient who tests positive is truly positive for a phenotype, and therefore is an indication of how much the test can be trusted clinically to reflect the phenotype. The sensitivity gives the probability that a patient who is positive actually tests positive.

In summary, a molecular method for risk stratification in PV that reflects clinical phenotype but also anticipates disease transformation has been identified. The presently disclosed subject matter provides a clinical assay that uses gene expression (Table 14) and a specific algorithm (Table 17) to identify those PV patients most likely to benefit from early institution of definitive therapy.

Example 11 Embodiment of a 10 Gene Panel Assay

The starting tissue can be either peripheral blood collected in standard EDTA vacutainer tubes or buffy coat cells isolated from a unit of whole blood.

For CD34+ cell isolation, peripheral blood mononuclear cells (PBMCs) are isolated from fresh samples by Ficoll-Paque (GE Healthcare Cat. No. 17-1440-03) density gradient centrifugation. CD34+ cells are isolated from the PBMCs using the Miltenyi Biotech CD34 Microbead Kit (Cat. No. 130-097-047) following the manufacturer's instructions. In an embodiment, the required amount of CD34+ cells is approximately 1-4×10⁶.

For optional CD34+ cell storage, purified CD34+ cells can be resuspended in freezing media (10% DMSO (Sigma Cat. No. D2650) 90% Fetal Bovine Serum (Gibco Cat. No. 26140)) and stored frozen at −80° C. using a slow cooling freezing unit (Thermo Scientific Cat. No. 5100-0001). Cells can also be transferred to liquid nitrogen for long term storage. Before RNA isolation, the cells are washed in Phosphate Buffered Saline pH 7.4 (Gibco Cat No. 10010-023) to remove all media.

For RNA isolation, RNA is extracted using the Qiagen RNeasy mini kit (Cat. No. 74104) with the QIA shredder (Cat. No. 79654) and on-column DNase treatment (Cat. No. 79254) following the manufacturer's instructions. Beta Actin levels (ACTB endogenous control; Applied Biosystems, Cat. No. 4333762F) for each sample are measured to determine if the concentration and quality was acceptable for further analysis. This assay is based upon a 10 gene signature and an algorithm (Table 17) which stratifies PV patients into indolent and aggressive forms of the disease. A qRT-PCR probability score of 5 or 6 indicates an aggressive form of PV. Each of the six described ratios must always be >2 to be scored as positive. Scores of 5/6 or 6/6 are considered indicative of an aggressive PV phenotype based on the supervised analysis of our initial gene expressing profiling results using top scoring pairs. Transcript expression levels are measured (in absolute copy numbers). The assay can be performed with a plurality of samples using a high throughput qRT-PCR platform.

Because this assay compares different genes within a single patient sample, absolute quantitation calculations are performed rather than compare relative expression levels. Therefore, plasmids containing either full length or partial cDNA of the targeted region for each gene are cloned and used to generate standard curves (FIG. 10). Once optimized, three standard dilutions can be chosen to use in the assay based upon the observed expression range of each gene. Copy numbers are calculated based on the known size and concentration of each plasmid. In addition to the standard curves and no template control, at least one patient sample with a previously determined qRT-PCR probability score is included in each run as a quality control.

Intra-assay precision is assessed by running all samples in duplicate. Replicate Ct values with standard deviations of greater than 0.5 are re-evaluated. Inter-assay precision is assessed by performing replicate assays on different days with fresh template cDNA from the same RNA sample of separate patients. In an example, the applied algorithm on samples from 8 patients generated the same call, either >4/6 or <5/6. In another example, four sets of patient samples using RNA extracted from CD34+ samples isolated from separate blood draws within the same twelve month period were run with no reported disease progression. Again, in each case there was no difference in the stratification of the patients using the methods of the presently disclosed subject matter.

In an example, the clinical sensitivity of the assay using 5-6/6 as indicative of an aggressive phenotype was 0.9. The clinical specificity of the assay using 5-6/6 as indicative of an aggressive phenotype was 1.0. The PPV at this threshold was 1.0 and the NPV was 0.95.

REFERENCES

All publications, patent applications, patents, and other references mentioned in the specification are indicative of the level of those skilled in the art to which the presently disclosed subject matter pertains. All publications, patent applications, patents, and other references are herein incorporated by reference to the same extent as if each individual publication, patent application, patent, and other reference was specifically and individually indicated to be incorporated by reference. It will be understood that, although a number of patent applications, patents, and other references are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.

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Although the foregoing subject matter has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be understood by those skilled in the art that certain changes and modifications can be practiced within the scope of the appended claims.

Tables

TABLE 1 QPCR using the Gene Expression GEX Assays GEX Target ABI GEX Gene Exon Assay ID Symbol Gene Name Boundaries Hs00188259_m1 WARS tryptophanyl-tRNA synthetase  9-10 Hs99999139_m1 TIMP1 TIMP metallopeptidase inhibitor 1 2-3 Hs00180737_m1 HPSE heparanase 8-9 Hs00172743_m1 DNTT deoxynucleotidyltransferase, terminal 10-11 Hs00181810_m1 CRHBP corticotropin releasing hormone binding protein 6-7 Hs00365956_m1 HOXA9 homeobox A9 1-2 Hs00202825_m1 SSBP2 single-stranded DNA binding protein 2 7-8 Hs00261238_m1 HOPX HOP homeobox 2-3 Hs99999905_m1 GAPDH glyceraldehyde-3-phosphate dehydrogenase 3-3 000397 miR-21 Human microRNA-21 (hsa-miR-21-5p) N/A 001093 RNU6B U6 small nuclear 2, small nuclear RNA N/A

TABLE 2 Polycythemia Vera Study Population Demographics Men (8) Women (11) Median Age 69 60 (years; range) (57-82)* (46-76) Median Disease Duration 11.5 9 (years; range) (1-28)* (1-18) Median JAK2 V617F 94 100 Neutrophil (55-100)* (60-100) Allele Burden (%; range) Median Hemoglobin 13.2 11.7 (gm %; range) (8.3-15.9)* (10.4-14.7) Median Leukocyte Count 16,690* 19,970 (10³/μL; range) (4430-177,190) (5080-50,070) Median Platelet Count 421,000** 948,000 (10³/μL; range) (151,000-810,000) (191,100-1,480,000) Median Spleen size 10.2 5.0 (cm; range) (0-32)* (0-20) *Not significantly different **p = 0.016

TABLE 3 Demographics and Clinical Features of the 19 Polycythemia Vera Patients at Study Entry Disease Leukocyte Platelet Spleen size (cm JAK2 V617F Age In Duration Hemoglobin count count below the left Neutro-phil Thrombosis/ Gender Years In Years (gm %) (10⁶/μL) (10⁶/μL) costal margin) Splenectomy allele burden (%) TIA Therapy M 74 7 12.9 17,620 388,000 32 No 100 No Phlebotomy, Anagrelide, Hydroxyurea, Busulfan M 66 20 8.3 177,190 454,000 25 Yes 100 Arterial Phlebotomy, Thalidomide, Cytoxan F 55 13 11.1 33,110 802,000 20 Yes 100 Portal and Phlebotomy, hepatic Hydroxyurea, veins; TIA Cytoxan, Anagrelide F 74 8 11.7 10,720 366,000 8 No 68 Hepatic Anagrelide, vein Hydroxyurea M 63 16 9.3 10,020 171,000 8 Yes 86 No Phlebotomy, Hydroxyurea F 48 18 10.4 50,070 1,017,000 5 Yes 100 Arterial Phlebotomy, and Hydroxyurea, venous Busulfan, Imatinib M 72 1 13.7 16,490 712,000 0 No 68 No Phlebotomy F 68 11 13.0 11,980 865,000 5 No 67 No Phlebotomy M 73 4 14.3 16,610 151,000 12.5 No 95 No Phlebotomy M 82 25 15.9 4,430 197,000 0 No 50 Arterial Phlebotomy, Hydroxyurea F 76 10 11.5 5,080 948,000 0 No 52 TIA Phlebotomy, Hydroxyurea M 57 4 13.6 19,970 810,000 0 No 88 No Phlebotomy F 57 12 13.0 19,530 1,119,000 8 No 60 No Phlebotomy, Hydroxyurea F 51 5 10.7 19,130 1,052,000 5 No 100 No Phlebotomy F 46 4 11.1 20,520 1,480,000 0 No 82 No Phlebotomy F 67 7 14.5 27,270 191,000 14 No 100 No Phlebotomy F 60 9 12.5 13,870 1,176,000 4 No 49 No Phlebotomy M 71 33 12.5 16,770 491,000 20 Yes 100 No Phlebotomy, Hydroxyurea

TABLE 4 Gene Expression in Women Patients Symbol (Na32 Gene Title (Na32 Entrez GeneID Adjusted ProbesetID consensus Mar13) consensus Mar13) (consensus Mar-13) Log2(FC) P-Value P-Value 204805_s_at H1FX H1 histone family, member X 8971 1.91935 0.00114 0.1019 202888_s_at ANPEP alanyl (membrane) 290 1.43197 0.001209 0.1019 aminopeptidase 213326_at VAMP1 vesicle-associated membrane 6843 1.380311 0.001564 0.1019 protein 1 (synaptobrevin 1) 212543_at AIM1 absent in melanoma 1 202 1.689059 0.002053 0.1019 201427_s_at SEPP1 selenoprotein P, plasma, 1 6414 1.427475 0.003366 0.125981 206674_at FLT3 fms-related tyrosine kinase 3 2322 1.701119 0.003846 0.125981 206385_s_at ANK3 ankyrin 3, node of Ranvier 288 1.257882 0.004488 0.125981 (ankyrin G) 209487_at RBPMS RNA binding protein with 11030 1.23478 0.00567 0.125981 multiple splicing 219871_at FLJ13197 uncharacterized FLJ13197 79667 1.301817 0.005704 0.125981 209488_s_at RBPMS RNA binding protein with 11030 1.275396 0.006845 0.125981 multiple splicing 221645_s_at ZNF83 zinc finger protein 83 55769 1.200283 0.007674 0.125981 213005_s_at KANK1 KN motif and ankyrin repeat 23189 1.707475 0.008166 0.125981 domains 1 213817_at IRAK3 interleukin-1 receptor- 11213 1.218239 0.010346 0.125981 associated kinase 3 202039_at MYO18A myosin XVIIIA 399687 1.175294 0.011058 0.125981 210644_s_at LAIR1 leukocyte-associated 3903 1.348313 0.011154 0.125981 immunoglobulin-like receptor 1 204352_at TRAF5 TNF receptor-associated factor 5 7188 1.125428 0.012268 0.125981 214290_s_at HIST2H2AA4 histone cluster 2, H2aa4 723790 1.879605 0.013116 0.125981 222146_s_at TCF4 transcription factor 4 6925 1.385756 0.013155 0.125981 59375_at MYO15B myosin XVB pseudogene 80022 1.108123 0.013372 0.125981 206486_at LAG3 lymphocyte-activation gene 3 3902 0.994363 0.014533 0.125981 212794_s_at KIAA1033 KIAA1033 23325 1.287389 0.014972 0.125981 218086_at NPDC1 neural proliferation, 56654 1.013593 0.015204 0.125981 differentiation and control, 1 218280_x_at HIST2H2AA4 histone cluster 2, H2aa4 723790 1.830191 0.01535 0.125981 213655_at YWHAE tyrosine 3- 7531 −1.40323 0.015549 0.125981 monooxygenase/tryptophan 5- monooxygenase activation protein, epsilon polypeptide 219173_at MYO15B myosin XVB pseudogene 80022 1.147267 0.016111 0.127919 212587_s_at PTPRC protein tyrosine phosphatase, 5788 1.942028 0.016627 0.128539 receptor type, C 218312_s_at ZSCAN18 zinc finger and SCAN domain 65982 1.539329 0.017836 0.128539 containing 18 207836_s_at RBPMS RNA binding protein with 11030 1.091491 0.018254 0.128539 multiple splicing 207426_s_at TNFSF4 tumor necrosis factor (ligand) 7292 1.381424 0.019204 0.129221 superfamily, member 4 212762_s_at TCF7L2 transcription factor 7-like 2 (T- 6934 1.046634 0.019813 0.129892 cell specific, HMG-box) 209398_at HIST1H1C histone cluster 1, H1c 3006 1.60555 0.020228 0.129892 211675_s_at MDFIC MyoD family inhibitor domain 29969 1.155886 0.020685 0.129892 containing 206133_at XAF1 XIAP associated factor 1 54739 1.158372 0.020857 0.129892 218966_at MYO5C myosin VC 55930 1.536923 0.02094 0.129892 214455_at HIST1H2BC histone cluster 1, H2bc 8347 1.482403 0.023205 0.131273 205471_s_at DACH1 dachshund homolog 1 1602 0.95962 0.023854 0.131273 (Drosophila) 218346_s_at SESN1 sestrin 1 27244 1.057229 0.024057 0.131273 209993_at ABCB1 ATP-binding cassette, sub- 5243 1.012543 0.024783 0.131273 family B (MDR/TAP), member 1 206710_s_at EPB41L3 erythrocyte membrane protein 23136 0.977202 0.024885 0.131273 band 4.1-like 3 202708_s_at HIST2H2BE histone cluster 2, H2be 8349 1.769114 0.02667 0.131273 200986_at SERPING1 serpin peptidase inhibitor, 710 1.048714 0.026758 0.131273 clade G (C1 inhibitor), member 1 207111_at EMR1 egf-like module containing, 2015 1.04867 0.026977 0.131273 mucin-like, hormone receptor- like 1 219355_at CXorf57 chromosome X open reading 55086 0.956366 0.027482 0.131273 frame 57 201196_s_at AMD1 adenosylmethionine 262 1.127364 0.02763 0.131273 decarboxylase 1 207564_x_at OGT O-linked N-acetylglucosamine 8473 1.180955 0.027642 0.131273 (GlcNAc) transferase 202686_s_at AXL AXL receptor tyrosine kinase 558 −1.17476 0.027808 0.131273 208268_at ADAM28 ADAM metallopeptidase 10863 1.222576 0.028106 0.131273 domain 28 215307_at ZNF529 zinc finger protein 529 57711 1.029099 0.028782 0.132865 219571_s_at ZNF12 zinc finger protein 12 7559 1.033403 0.030225 0.136525 209994_s_at ABCB1 ATP-binding cassette, sub- 5243 0.988532 0.030956 0.136933 family B (MDR/TAP), member 1 212560_at SORL1 sortilin-related receptor, 6653 1.232375 0.031193 0.136933 L(DLR class) A repeats containing 205767_at EREG epiregulin 2069 1.576209 0.032309 0.137923 221718_s_at AKAP13 A kinase (PRKA) anchor 11214 0.990575 0.033371 0.139481 protein 13 214472_at HIST1H2AD histone cluster 1, H2ad 3013 1.221696 0.034306 0.139481 209447_at SYNE1 spectrin repeat containing, 23345 1.026492 0.034672 0.139481 nuclear envelope 1 207571_x_at THEMIS2 thymocyte selection associated 9473 1.23688 0.035236 0.139481 family member 2 210785_s_at THEMIS2 thymocyte selection associated 9473 1.258674 0.035631 0.139481 family member 2 209543_s_at CD34 CD34 molecule 947 1.31764 0.037479 0.144458 220952_s_at PLEKHA5 pleckstrin homology domain 54477 1.059186 0.039091 0.147854 containing, family A member 5 201448_at TIA1 TIA1 cytotoxic granule- 7072 1.289342 0.039105 0.147854 associated RNA binding protein 221543_s_at ERLIN2 ER lipid raft associated 2 11160 1.019463 0.040859 0.150196 206715_at TFEC transcription factor EC 22797 1.291151 0.042627 0.153844 220122_at MCTP1 multiple C2 domains, 79772 1.025269 0.043486 0.155532 transmembrane 1 209318_x_at PLAGL1 pleiomorphic adenoma gene- 5325 1.315505 0.046285 0.160061 like 1 208056_s_at CBFA2T3 core-binding factor, runt 863 1.116738 0.04637 0.160061 domain, alpha subunit 2; translocated to, 3 204972_at OAS2 2′-5′-oligoadenylate synthetase 4939 1.090829 0.046707 0.160061 2, 69/71 kDa 201236_s_at BTG2 BTG family, member 2 7832 1.091134 0.046768 0.160061 214218_s_at XIST X inactive specific transcript 7503 1.3244 0.04853 0.163276 (non-protein coding) 220940_at ANKRD36B ankyrin repeat domain 36B 57730 1.168735 0.049352 0.163699 209930_s_at NFE2 nuclear factor (erythroid- 4778 1.331755 0.050315 0.163699 derived 2), 45 kDa 205239_at AREG amphiregulin 374 1.205571 0.051692 0.163838 217593_at ZSCAN18 zinc finger and SCAN domain 65982 0.840704 0.054078 0.167551 containing 18 222067_x_at HIST1H2BD histone cluster 1, H2bd 3017 1.198697 0.063984 0.189566 213094_at GPR126 G protein-coupled receptor 126 57211 1.17747 0.06522 0.191029 212775_at OBSL1 obscurin-like 1 23363 1.331391 0.065586 0.191029 221249_s_at FAM117A family with sequence similarity 81558 1.637593 0.066403 0.191029 117, member A 210172_at SF1 splicing factor 1 7536 0.997588 0.067011 0.191391 207496_at MS4A2 membrane-spanning 4- 2206 0.772601 0.069284 0.193702 domains, subfamily A, member 2 218589_at LPAR6 lysophosphatidic acid receptor 6 10161 1.080018 0.071983 0.199841 204749_at NAP1L3 nucleosome assembly protein 4675 1.296406 0.073554 0.202786 1-like 3 211302_s_at PDE4B phosphodiesterase 4B, cAMP- 5142 0.858839 0.076239 0.207306 specific 215779_s_at HIST1H2BG histone cluster 1, H2bg 8339 0.902184 0.076987 0.207917 213293_s_at TRIM22 tripartite motif containing 22 10346 1.468514 0.077535 0.207984 218352_at RCBTB1 regulator of chromosome 55213 1.08448 0.082823 0.214891 condensation (RCC1) and BTB (POZ) domain containing protein 1 220918_at RUNX1-IT1 RUNX1 intronic transcript 1 80215 1.110688 0.083008 0.214891 (non-protein coding) 204116_at IL2RG interleukin 2 receptor, gamma 3561 0.892953 0.085322 0.217134 210254_at MS4A3 membrane-spanning 4- 932 1.032003 0.088393 0.223517 domains, subfamily A, member 3 (hematopoietic cell-specific) 213998_s_at DDX17 DEAD (Asp-Glu-Ala-Asp) box 10521 1.29709 0.090384 0.225675 helicase 17 206631_at PTGER2 prostaglandin E receptor 2 5732 0.863461 0.094568 0.233189 (subtype EP2), 53 kDa 219737_s_at PCDH9 protocadherin 9 5101 1.423384 0.095952 0.235143 206067_s_at WT1 Wilms tumor 1 7490 −0.97509 0.097098 0.235189 212813_at JAM3 junctional adhesion molecule 3 83700 0.851683 0.097156 0.235189 203708_at PDE4B phosphodiesterase 4B, cAMP- 5142 1.258787 0.098941 0.236778 specific 213734_at WSB2 WD repeat and SOCS box 55884 −1.03595 0.103178 0.243147 containing 2 212382_at TCF4 transcription factor 4 6925 1.222721 0.103506 0.243147 212044_s_at RPL27A ribosomal protein L27a 6157 −1.30359 0.11014 0.255203 209774_x_at CXCL2 chemokine (C-X-C motif) 2920 −1.35733 0.111447 0.255748 ligand 2 204420_at FOSL1 FOS-like antigen 1 8061 0.777712 0.125065 0.28372 219352_at HERC6 HECT and RLD domain 55008 0.731325 0.126978 0.286421 containing E3 ubiquitin protein ligase family member 6 219371_s_at KLF2 Kruppel-like factor 2 (lung) 10365 0.952494 0.133808 0.29512 208436_s_at IRF7 interferon regulatory factor 7 3665 0.817301 0.142117 0.308309 208490_x_at HIST1H2BF histone cluster 1, H2bf 8343 0.823714 0.153384 0.325493 217168_s_at HERPUD1 homocysteine-inducible, 9709 −1.02032 0.153554 0.325493 endoplasmic reticulum stress- inducible, ubiquitin-like domain member 1 218723_s_at RGCC regulator of cell cycle 28984 1.178353 0.16831 0.347202 221943_x_at RPL38 ribosomal protein L38 6169 −0.87537 0.169666 0.347202 202912_at ADM adrenomedullin 133 −0.90139 0.175228 0.356746 202086_at MX1 myxovirus (influenza virus) 4599 1.082812 0.179388 0.362009 resistance 1, interferon- inducible protein p78 (mouse) 204794_at DUSP2 dual specificity phosphatase 2 1844 −1.05607 0.185851 0.370769 200878_at EPAS1 endothelial PAS domain 2034 −0.94127 0.187138 0.371469 protein 1 214395_x_at EEF1D eukaryotic translation 1936 −0.75421 0.221404 0.418581 elongation factor 1 delta (guanine nucleotide exchange protein) 39248_at AQP3 aquaporin 3 (Gill blood group) 360 −1.0387 0.221416 0.418581 201590_x_at ANXA2 annexin A2 302 −0.83364 0.224539 0.422475 202087_s_at CTSL1 cathepsin L1 1514 −0.72277 0.227535 0.426091 201897_s_at CKS1B CDC28 protein kinase 1163 −0.75777 0.23559 0.436077 regulatory subunit 1B 202869_at OAS1 2′-5′-oligoadenylate synthetase 4938 0.645604 0.239395 0.44 1, 40/46 kDa 204351_at S100P S100 calcium binding protein P 6286 −1.19041 0.248298 0.447645 205220_at HCAR3 hydroxycarboxylic acid 8843 −0.75269 0.248929 0.447645 receptor 3 201289_at CYR61 cysteine-rich, angiogenic 3491 −0.94996 0.249241 0.447645 inducer, 61 213943_at TWIST1 twist basic helix-loop-helix 7291 −0.76051 0.251394 0.447645 transcription factor 1 201566_x_at ID2 inhibitor of DNA binding 2, 3398 0.738645 0.252916 0.448249 dominant negative helix-loop- helix protein 204286_s_at PMAIP1 phorbol-12-myristate-13- 5366 0.658217 0.254968 0.449876 acetate-induced protein 1 203038_at PTPRK protein tyrosine phosphatase, 5796 −0.89732 0.259282 0.450102 receptor type, K 212097_at CAV1 caveolin 1, caveolae protein, 857 −0.8953 0.259704 0.450102 22 kDa 202733_at P4HA2 prolyl 4-hydroxylase, alpha 8974 −0.88547 0.260765 0.450102 polypeptide II 203917_at CXADR coxsackie virus and adenovirus 1525 −0.70323 0.261975 0.450233 receptor 204103_at CCL4 chemokine (C-C motif) ligand 4 6351 −0.93799 0.264919 0.453331 202458_at PRSS23 protease, serine, 23 11098 −0.75062 0.266945 0.454838 213539_at CD3D CD3d molecule, delta (CD3- 915 −0.74368 0.268679 0.455836 TCR complex) 210321_at GZMH granzyme H (cathepsin G-like 2999 −0.6763 0.279967 0.472525 2, protein h-CCPX) 214453_s_at IFI44 interferon-induced protein 44 10561 0.80743 0.280897 0.472525 211560_s_at ALAS2 aminolevulinate, delta-, 212 −0.96058 0.293731 0.486931 synthase 2 201744_s_at LUM lumican 4060 −0.72481 0.298238 0.491288 211340_s_at MCAM melanoma cell adhesion 4162 −0.77567 0.306814 0.499201 molecule 204959_at MNDA myeloid cell nuclear 4332 −0.90022 0.316701 0.504456 differentiation antigen 202587_s_at AK1 adenylate kinase 1 203 −0.63641 0.317949 0.504456 218959_at HOXC10 homeobox C10 3226 −0.61573 0.319085 0.504456 205495_s_at GNLY granulysin 10578 −0.68517 0.320209 0.504456 221958_s_at WLS wntless homolog (Drosophila) 79971 −0.70884 0.324929 0.50696 202688_at TNFSF10 tumor necrosis factor (ligand) 8743 0.618043 0.325629 0.50696 superfamily, member 10 209087_x_at MCAM melanoma cell adhesion 4162 −0.81432 0.326954 0.507034 molecule 209210_s_at FERMT2 fermitin family member 2 10979 −1.11824 0.329723 0.50854 205488_at GZMA granzyme A (granzyme 1, 3001 −0.59006 0.330487 0.50854 cytotoxic T-lymphocyte- associated serine esterase 3) 201739_at SGK1 serum/glucocorticoid regulated 6446 −1.0293 0.335357 0.508988 kinase 1 211506_s_at IL8 interleukin 8 3576 −0.69682 0.336251 0.508988 204962_s_at CENPA centromere protein A 1058 −0.67424 0.336317 0.508988 212698_s_at 10-Sep septin 10 151011 −0.74724 0.337188 0.508988 33322_i_at SFN stratifin 2810 −0.75401 0.341463 0.509458 218705_s_at SNX24 sorting nexin 24 28966 −0.57987 0.342374 0.509458 205552_s_at OAS1 2′-5′-oligoadenylate synthetase 4938 0.50836 0.344124 0.509458 1, 40/46 kDa 201506_at TGFBI transforming growth factor, 7045 −0.66233 0.345804 0.509458 beta-induced, 68 kDa 202011_at TJP1 tight junction protein 1 7082 −0.64431 0.347774 0.509458 204517_at PPIC peptidylprolyl isomerase C 5480 −0.59936 0.349374 0.509458 (cyclophilin C) 209230_s_at NUPR1 nuclear protein, transcriptional 26471 −0.65323 0.350449 0.509458 regulator, 1 219073_s_at OSBPL10 oxysterol binding protein-like 114884 −0.59261 0.351262 0.509458 10 205476_at CCL20 chemokine (C-C motif) ligand 6364 −0.6399 0.357651 0.512993 20 221577_x_at GDF15 growth differentiation factor 15 9518 −0.65491 0.364519 0.516042 202718_at IGFBP2 insulin-like growth factor 3485 −0.57195 0.365259 0.516042 binding protein 2, 36 kDa 207039_at CDKN2A cyclin-dependent kinase 1029 −0.71306 0.36807 0.517873 inhibitor 2A 204920_at CPS1 carbamoyl-phosphate synthase 1373 −0.81774 0.369164 0.517873 1, mitochondrial 200771_at LAMC1 laminin, gamma 1 (formerly 3915 −0.65676 0.37062 0.518085 LAMB2) 219454_at EGFL6 EGF-like-domain, multiple 6 25975 −0.56974 0.374512 0.518966 212328_at LIMCH1 LIM and calponin homology 22998 −0.72538 0.37555 0.518966 domains 1 207076_s_at ASS1 argininosuccinate synthase 1 445 −0.96506 0.376479 0.518966 201983_s_at EGFR epidermal growth factor 1956 −0.56631 0.379717 0.519326 receptor 203438_at STC2 stanniocalcin 2 8614 −0.54868 0.385726 0.520981 212012_at PXDN peroxidasin homolog 7837 −0.69905 0.3859 0.520981 (Drosophila) 203153_at IFIT1 interferon-induced protein with 3434 0.55537 0.389138 0.520981 tetratricopeptide repeats 1 206785_s_at KLRC1 killer cell lectin-like receptor 3821 −0.5784 0.393476 0.520981 subfamily C, member 1 217564_s_at CPS1 carbamoyl-phosphate synthase 1373 −0.79731 0.394672 0.520981 1, mitochondrial 202052_s_at RAI14 retinoic acid induced 14 26064 −0.5724 0.3967 0.520981 204992_s_at PFN2 profilin 2 5217 −0.772 0.396957 0.520981 204007_at FCGR3B Fc fragment of IgG, low 2215 −0.64158 0.397187 0.520981 affinity IIIb, receptor (CD16b) 210095_s_at IGFBP3 insulin-like growth factor 3486 −0.60033 0.397625 0.520981 binding protein 3 200798_x_at MCL1 myeloid cell leukemia 4170 0.540947 0.39956 0.521124 sequence 1 (BCL2-related) 212364_at MYO1B myosin IB 4430 −0.55526 0.401476 0.521124 212765_at CAMSAP2 calmodulin regulated spectrin- 23271 −0.56269 0.401672 0.521124 associated protein family, member 2 204284_at PPP1R3C protein phosphatase 1, 5507 −0.54464 0.406184 0.523753 regulatory subunit 3C 201976_s_at MYO10 myosin X 4651 −0.55951 0.406337 0.523753 208079_s_at AURKA aurora kinase A 6790 −0.65513 0.408025 0.524226 219959_at MOCOS molybdenum cofactor sulfurase 55034 −0.85667 0.410521 0.525731 213139_at SNAI2 snail homolog 2 (Drosophila) 6591 −0.55315 0.414603 0.526676 201292_at TOP2A topoisomerase (DNA) II alpha 7153 −0.61773 0.41473 0.526676 170 kDa 209101_at CTGF connective tissue growth factor 1490 −0.63969 0.416358 0.526676 210587_at INHBE inhibin, beta E 83729 −0.61908 0.419791 0.526676 202768_at FOSB FBJ murine osteosarcoma viral 2354 0.785327 0.421407 0.526676 oncogene homolog B 219148_at PBK PDZ binding kinase 55872 −0.62389 0.422616 0.526676 201505_at LAMB1 laminin, beta 1 3912 −0.59203 0.422812 0.526676 204439_at IFI44L interferon-induced protein 44- 10964 0.779572 0.423198 0.526676 like 204688_at SGCE sarcoglycan, epsilon 8910 −0.53807 0.427632 0.530004 210274_at MAGEA8 melanoma antigen family A, 8 4107 −0.55437 0.440077 0.53411 218400_at OAS3 2′-5′-oligoadenylate synthetase 4940 0.401878 0.441825 0.53411 3, 100 kDa 204033_at TRIP13 thyroid hormone receptor 9319 −0.53242 0.443536 0.53411 interactor 13 205033_s_at DEFA1 defensin, alpha 1 1667 −0.68446 0.443688 0.53411 209921_at SLC7A11 solute carrier family 7 (anionic 23657 −0.67363 0.443971 0.53411 amino acid transporter light chain, xc- system), member 11 204415_at IFI6 interferon, alpha-inducible 2537 0.448113 0.446822 0.53412 protein 6 203510_at MET met proto-oncogene 4233 −0.59266 0.449267 0.53412 (hepatocyte growth factor receptor) 33323_r_at SFN stratifin 2810 −0.63466 0.450623 0.53412 212671_s_at HLA-DQA1 major histocompatibility 3117 −0.73617 0.45086 0.53412 complex, class II, DQ alpha 1 205047_s_at ASNS asparagine synthetase 440 −0.62208 0.454871 0.534967 (glutamine-hydrolyzing) 200606_at DSP desmoplakin 1832 −0.6615 0.455463 0.534967 205573_s_at SNX7 sorting nexin 7 51375 −0.50744 0.460196 0.538931 204684_at NPTX1 neuronal pentraxin I 4884 −0.48978 0.463571 0.540181 204483_at ENO3 enolase 3 (beta, muscle) 2027 −0.57582 0.463984 0.540181 221008_s_at AGXT2L1 alanine-glyoxylate 64850 −0.59789 0.471814 0.545637 aminotransferase 2-like 1 200795_at SPARCL1 SPARC-like 1 (hevin) 8404 −0.50481 0.475562 0.546517 211618_s_at ALPI alkaline phosphatase, intestinal 248 −0.48827 0.477352 0.546517 207140_at ALPI alkaline phosphatase, intestinal 248 −0.90959 0.477868 0.546517 204288_s_at SORBS2 sorbin and SH3 domain 8470 −0.52462 0.481567 0.546517 containing 2 201681_s_at DLG5 discs, large homolog 5 9231 −0.47202 0.48294 0.546517 (Drosophila) 203881_s_at DMD dystrophin 1756 −0.49504 0.483193 0.546517 219599_at EIF4B eukaryotic translation initiation 1975 −0.53684 0.487369 0.548489 factor 4B 203636_at MID1 midline 1 (Opitz/BBB 4281 −0.45754 0.488315 0.548489 syndrome) 214240_at GAL galanin/GMAP prepropeptide 51083 −0.50116 0.489081 0.548489 209094_at DDAH1 dimethylarginine 23576 −0.51772 0.495452 0.554068 dimethylaminohydrolase 1 218631_at AVPI1 arginine vasopressin-induced 1 60370 −0.49809 0.500208 0.556142 204540_at EEF1A2 eukaryotic translation 1917 −0.42637 0.500471 0.556142 elongation factor 1 alpha 2 210016_at MYT1L myelin transcription factor 1- 23040 −0.55739 0.502376 0.556142 like 205289_at BMP2 bone morphogenetic protein 2 650 −0.51385 0.50342 0.556142 205751_at SH3GL2 SH3-domain GRB2-like 2 6456 −0.43617 0.50431 0.556142 218541_s_at C8orf4 chromosome 8 open reading 56892 −0.52893 0.509174 0.559951 frame 4 214247_s_at DKK3 dickkopf 3 homolog (Xenopus 27122 −0.51465 0.511216 0.560643 laevis) 214212_x_at FERMT2 fermitin family member 2 10979 −0.44903 0.514141 0.562297 208209_s_at C4BPB complement component 4 725 −0.49739 0.518251 0.565235 binding protein, beta 208396_s_at PDE1A phosphodiesterase 1A, 5136 −0.46854 0.526142 0.571827 calmodulin-dependent 209942_x_at MAGEA3 melanoma antigen family A, 3 4102 −0.58148 0.5289 0.572135 214612_x_at MAGEA6 melanoma antigen family A, 6 4105 −0.60458 0.532798 0.57304 201660_at ACSL3 acyl-CoA synthetase long- 2181 −0.42544 0.533497 0.57304 chain family member 3 204975_at EMP2 epithelial membrane protein 2 2013 −0.47324 0.536232 0.57304 201667_at GJA1 gap junction protein, alpha 1, 2697 −0.55978 0.536604 0.57304 43 kDa 201291_s_at TOP2A topoisomerase (DNA) II alpha 7153 −0.51625 0.536954 0.57304 170 kDa 204653_at TFAP2A transcription factor AP-2 alpha 7020 −0.43406 0.544838 0.579895 (activating enhancer binding protein 2 alpha) 205132_at ACTC1 actin, alpha, cardiac muscle 1 70 −0.38632 0.55232 0.584901 217127_at CTH cystathionase (cystathionine 1491 −0.44229 0.552489 0.584901 gamma-lyase) 205381_at LRRC17 leucine rich repeat containing 17 10234 −0.39955 0.554073 0.585019 209967_s_at CREM cAMP responsive element 1390 −0.45103 0.557616 0.587198 modulator 202672_s_at ATF3 activating transcription factor 3 467 0.490404 0.560082 0.587586 209631_s_at GPR37 G protein-coupled receptor 37 2861 −0.44217 0.560945 0.587586 (endothelin receptor type B- like) 221730_at COL5A2 collagen, type V, alpha 2 1290 −0.40443 0.562469 0.587632 210467_x_at MAGEA12 melanoma antigen family A, 12 4111 −0.46503 0.566943 0.590752 203083_at THBS2 thrombospondin 2 7058 −0.37936 0.569007 0.59135 215034_s_at TM4SF1 transmembrane 4 L six family 4071 −0.4484 0.571318 0.592202 member 1 206377_at FOXF2 forkhead box F2 2295 −0.36443 0.585328 0.605143 213131_at OLFM1 olfactomedin 1 10439 −0.35953 0.610643 0.629676 202976_s_at RHOBTB3 Rho-related BTB domain 22836 −0.3467 0.614674 0.63219 containing 3 202887_s_at DDIT4 DNA-damage-inducible 54541 −0.45548 0.618537 0.63452 transcript 4 203984_s_at CASP9 caspase 9, apoptosis-related 842 −0.35376 0.632586 0.647259 cysteine peptidase 205290_s_at BMP2 bone morphogenetic protein 2 650 −0.47882 0.640799 0.653977 204337_at RGS4 regulator of G-protein 5999 −0.26477 0.708833 0.717874 signaling 4 217867_x_at BACE2 beta-site APP-cleaving enzyme 2 25825 −0.2906 0.71423 0.721499 212327_at LIMCH1 LIM and calponin homology 22998 −0.28139 0.723086 0.728591 domains 1 202391_at BASP1 brain abundant, membrane 10409 0.338672 0.73503 0.738752 attached signal protein 1

TABLE 5 Gene Expression in Men Patients Probe Symbol (Na32 Gene Title (Na32 Entrez Gene ID Adjusted set ID consensus Mar13) consensus Mar13) (consensus Mar-13) Log2 (FC) P-Value p-Value 208730_x_at RAB2A RAB2A, member RAS 5862 −2.23913 0.00173 0.22461 oncogene family 201242_s_at ATP1B1 ATPase, Na+/K+ transporting, 481 −2.30995 0.001936 0.22461 beta 1 polypeptide 206857_s_at FKBP1B FK506 binding protein 1B, 2281 −2.18904 0.003742 0.22461 12.6 kDa 208636_at ACTN1 actinin, alpha 1 87 −1.91968 0.005679 0.22461 206493_at ITGA2B integrin, alpha 2b (platelet 3674 −2.94275 0.006689 0.22461 glycoprotein IIb of IIb/IIIa complex, antigen CD41) 211986_at AHNAK AHNAK nucleoprotein 79026 1.54422 0.00875 0.22461 203509_at SORL1 sortilin-related receptor, 6653 1.561462 0.009157 0.22461 L(DLR class) A repeats containing 206494_s_at ITGA2B integrin, alpha 2b (platelet 3674 −3.20741 0.009481 0.22461 glycoprotein IIb of IIb/IIIa complex, antigen CD41) 201846_s_at RYBP RING1 and YY1 binding 23429 −1.62523 0.009701 0.22461 protein 213229_at DICER1 dicer 1, ribonuclease type III 23405 −1.70923 0.010255 0.22461 202620_s_at PLOD2 procollagen-lysine, 2- 5352 −1.86792 0.010535 0.22461 oxoglutarate 5-dioxygenase 2 202760_s_at AKAP2 A kinase (PRKA) anchor 11217 −1.66558 0.010984 0.22461 protein 2 215813_s_at PTGS1 prostaglandin-endoperoxide 5742 −2.12304 0.011371 0.22461 synthase 1 (prostaglandin G/H synthase and cyclooxygenase) 219054_at NPR3 natriuretic peptide receptor 4883 1.815762 0.012117 0.22461 C/guanylate cyclase C (atrionatriuretic peptide receptor C) 37462_i_at SF3A2 splicing factor 3a, subunit 2, 8175 −1.73475 0.01271 0.22461 66 kDa 212266_s_at SRSF5 serine/arginine-rich splicing 6430 1.814328 0.012914 0.22461 factor 5 201489_at PPIF peptidylprolyl isomerase F 10105 −1.57807 0.013197 0.22461 203096_s_at RAPGEF2 Rap guanine nucleotide 9693 −1.90184 0.013308 0.22461 exchange factor (GEF) 2 205128_x_at PTGS1 prostaglandin-endoperoxide 5742 −1.98263 0.013941 0.22461 synthase 1 (prostaglandin G/H synthase and cyclooxygenase) 221059_s_at COTL1 coactosin-like 1 23406 −2.38475 0.014419 0.22461 (Dictyostelium) 212268_at SERPINB1 serpin peptidase inhibitor, clade 1992 1.576065 0.015209 0.22461 B (ovalbumin), member 1 201012_at ANXA1 annexin Al 301 1.431866 0.015821 0.22461 207808_s_at PROS1 protein S (alpha) 5627 −2.54684 0.01834 0.22461 206302_s_at NUDT4 nudix (nucleoside diphosphate 11163 −1.35819 0.01853 0.22461 linked moiety X)-type motif 4 203320_at SH2B3 SH2B adaptor protein 3 10019 −1.48125 0.019452 0.22461 205647_at RAD52 RAD52 homolog (S. 5893 1.244884 0.019524 0.22461 cerevisiae) 210105_s_at FYN FYN oncogene related to SRC, 2534 −1.57809 0.020057 0.22461 FGR, YES 200598_s_at HSP90B1 heat shock protein 90 kDa beta 7184 −1.77815 0.020317 0.22461 (Grp94), member 1 200964_at UBA1 ubiquitin-like modifier 7317 −1.39778 0.020397 0.22461 activating enzyme 1 221493_at TSPYL1 TSPY-like 1 7259 1.744517 0.021178 0.22461 206174_s_at PPP6C protein phosphatase 6, catalytic 5537 −1.35248 0.021364 0.22461 subunit 202284_s_at CDKN1A cyclin-dependent kinase 1026 −2.00033 0.023319 0.22461 inhibitor 1A (p21, Cip1) 206207_at CLC Charcot-Leyden crystal protein 1178 −1.88811 0.023511 0.22461 206655_s_at GP1BB glycoprotein Ib (platelet), beta 2812 −2.92989 0.023514 0.22461 polypeptide 206571_s_at MAP4K4 mitogen-activated protein 9448 −1.25865 0.02388 0.22461 kinase kinase kinase kinase 4 209651_at TGFB1I1 transforming growth factor beta 7041 −2.18243 0.024567 0.22461 1 induced transcript 1 204689_at HHEX hematopoietically expressed 3087 1.462027 0.024863 0.22461 homeobox 205067_at IL1B interleukin 1, beta 3553 1.255404 0.025653 0.22461 203380_x_at SRSF5 serine/arginine-rich splicing 6430 1.503237 0.025756 0.22461 factor 5 200923_at LGALS3BP lectin, galactoside-binding, 3959 −1.56076 0.025836 0.22461 soluble, 3 binding protein 202949_s_at FHL2 four and a half LIM domains 2 2274 −1.37209 0.026399 0.22461 201695_s_at PNP purine nucleoside 4860 −1.41068 0.026458 0.22461 phosphorylase 220748_s_at ZNF580 zinc finger protein 580 51157 −1.34215 0.028123 0.22461 217901_at DSG2 desmoglein 2 1829 1.320976 0.028803 0.22461 219798_s_at MEPCE methylphosphate capping 56257 −1.33001 0.029245 0.22461 enzyme 209381_x_at SF3A2 splicing factor 3a, subunit 2, 8175 −1.41034 0.029259 0.22461 66 kDa 204222_s_at GLIPR1 GLI pathogenesis-related 1 11010 1.439903 0.030437 0.22461 221004_s_at ITM2C integral membrane protein 2C 81618 1.219859 0.030753 0.22461 206049_at SELP selectin P (granule membrane 6403 −2.17111 0.031111 0.22461 protein 140 kDa, antigen CD62) 37966_at PARVB parvin, beta 29780 −2.06542 0.031383 0.22461 219681_s_at RAB11FIP1 RAB11 family interacting 80223 −1.35248 0.031529 0.22461 protein 1 (class I) 212242_at TUBA4A tubulin, alpha 4a 7277 −2.39641 0.03153 0.22461 218237_s_at SLC38A1 solute carrier family 38, 81539 1.547237 0.032294 0.22461 member 1 213726_x_at TUBB4B tubulin, beta 4B class IVb 10383 −1.30164 0.032486 0.22461 39402_at IL1B interleukin 1, beta 3553 1.235287 0.032639 0.22461 209820_s_at TBL3 transducin (beta)-like 3 10607 −1.20712 0.032649 0.22461 212312_at BCL2L1 BCL2-like 1 598 −1.39562 0.033632 0.22461 211600_at PTPRO protein tyrosine phosphatase, 5800 −1.45225 0.03416 0.22461 receptor type, O 214783_s_at ANXA11 annexin A11 311 −1.22688 0.034175 0.22461 200616_s_at MLEC malectin 9761 −1.20495 0.034386 0.22461 211926_s_at MYH9 myosin, heavy chain 9, non- 4627 −1.2641 0.034926 0.22461 muscle 202059_s_at KPNA1 karyopherin alpha 1 (importin 3836 −1.12248 0.034962 0.22461 alpha 5) 221899_at N4BP2L2 NEDD4 binding protein 2-like 2 10443 1.316587 0.035008 0.22461 210347_s_at BCL11A B-cell CLL/lymphoma 11A 53335 1.273905 0.035019 0.22461 (zinc finger protein) 221748_s_at TNS1 tensin 1 7145 −1.4894 0.035747 0.22461 203940_s_at VASH1 vasohibin 1 22846 −1.35628 0.037032 0.22461 204610_s_at CCDC85B coiled-coil domain containing 85B 11007 −1.5951 0.037663 0.22461 222231_s_at LRRC59 leucine rich repeat containing 59 55379 −1.11855 0.038092 0.22461 212177_at PNISR PNN-interacting 25957 1.175547 0.038211 0.22461 serine/arginine-rich protein 201692_at SIGMAR1 sigma non-opioid intracellular 10280 −1.06876 0.038307 0.22461 receptor 1 202112_at VWF von Willebrand factor 7450 −1.36382 0.039327 0.22461 206310_at SPINK2 serine peptidase inhibitor, 6691 1.568851 0.039466 0.22461 Kazal type 2 (acrosin-trypsin inhibitor) 218899_s_at BAALC brain and acute leukemia, 79870 1.51143 0.039771 0.22461 cytoplasmic 208308_s_at GPI glucose-6-phosphate isomerase 2821 −1.24247 0.040139 0.22461 221834_at LONP2 lon peptidase 2, peroxisomal 83752 1.261036 0.040303 0.22461 210719_s_at HMG20B high mobility group 20B 10362 −1.39762 0.040525 0.22461 200808_s_at ZYX zyxin 7791 −1.54764 0.041293 0.22461 209945_s_at GSK3B glycogen synthase kinase 3 2932 −1.28118 0.041713 0.22461 beta 208637_x_at ACTN1 actinin, alpha 1 87 −1.74284 0.041994 0.22461 209088_s_at UBN1 ubinuclein 1 29855 −1.14187 0.042143 0.22461 211005_at LAT linker for activation of T cells 27040 −1.83145 0.042364 0.22461 218131_s_at GATAD2A GATA zinc finger domain 54815 −1.22531 0.042653 0.22461 containing 2A 202729_s_at LTBP1 latent transforming growth 4052 −1.87245 0.042694 0.22461 factor beta binding protein 1 219357_at GTPBP1 GTP binding protein 1 9567 −1.11964 0.042776 0.22461 201980_s_at RSU1 Ras suppressor protein 1 6251 −1.33636 0.043967 0.22461 211671_s_at NR3C1 nuclear receptor subfamily 3, 2908 1.257541 0.044183 0.22461 group C, member 1 (glucocorticoid receptor) 203007_x_at LYPLA1 lysophospholipase I 10434 −1.24485 0.04487 0.22461 210299_s_at FHL1 four and a half LIM domains 1 2273 1.459962 0.045279 0.22461 210783_x_at CLEC11A C-type lectin domain family 6320 −1.14617 0.045531 0.22461 11, member A 209154_at TAX1BP3 Tax1 (human T-cell leukemia 30851 −1.80171 0.045558 0.22461 virus type I) binding protein 3 212279_at TMEM97 transmembrane protein 97 27346 −1.20825 0.046373 0.22461 202102_s_at BRD4 bromodomain containing 4 23476 −1.31832 0.046377 0.22461 200719_at SKP1 S-phase kinase-associated 6500 −1.18511 0.046416 0.22461 protein 1 213416_at ITGA4 integrin, alpha 4 (antigen 3676 1.500306 0.046971 0.22461 CD49D, alpha 4 subunit of VLA-4 receptor) 201251_at PKM pyruvate kinase, muscle 5315 −1.61415 0.04732 0.22461 220094_s_at CCDC90A coiled-coil domain containing 63933 −1.33066 0.048464 0.22461 90A 202275_at G6PD glucose-6-phosphate 2539 −1.46785 0.04883 0.22461 dehydrogenase 214146_s_at PPBP pro-platelet basic protein 5473 −2.44242 0.049566 0.22461 (chemokine (C-X-C motif) ligand 7) 204081_at NRGN neurogranin (protein kinase C 4900 −2.56374 0.049579 0.22461 substrate, RC3) 209868_s_at RBMS1 RNA binding motif, single 5937 1.165728 0.050155 0.22461 stranded interacting protein 1 211922_s_at CAT catalase 847 1.232958 0.051088 0.22461 222310_at SCAF4 SR-related CTD-associated 57466 1.077534 0.05119 0.22461 factor 4 200697_at HK1 hexokinase 1 3098 −1.1627 0.051949 0.22461 200706_s_at LITAF lipopolysaccharide-induced 9516 1.091394 0.052104 0.22461 TNF factor 220964_s_at RAB1B RAB1B, member RAS 81876 −1.24067 0.052429 0.22461 oncogene family 210215_at TFR2 transferrin receptor 2 7036 −1.65926 0.052589 0.22461 201260_s_at SYPL1 synaptophysin-like 1 6856 1.519931 0.052716 0.22461 221771_s_at MPHOSPH8 M-phase phosphoprotein 8 54737 1.277564 0.053033 0.22461 210986_s_at TPM1 tropomyosin 1 (alpha) 7168 −1.54226 0.053308 0.22461 203674_at HELZ helicase with zinc finger 9931 1.115528 0.053318 0.22461 207238_s_at PTPRC protein tyrosine phosphatase, 5788 1.189131 0.053365 0.22461 receptor type, C 201864_at GDI1 GDP dissociation inhibitor 1 2664 −1.17328 0.053513 0.22461 212036_s_at PNN pinin, desmosome associated 5411 1.514285 0.053837 0.22461 protein 213521_at PTPN18 protein tyrosine phosphatase, 26469 −1.32436 0.05412 0.22461 non-receptor type 18 (brain- derived) 202644_s_at TNFAIP3 tumor necrosis factor, alpha- 7128 −1.72075 0.054213 0.22461 induced protein 3 219090_at SLC24A3 solute carrier family 24 57419 −1.33752 0.054392 0.22461 (sodium/potassium/calcium exchanger), member 3 209117_at WBP2 WW domain binding protein 2 23558 −1.30969 0.054585 0.22461 209160_at AKR1C3 aldo-keto reductase family 1, 8644 1.332339 0.054731 0.22461 member C3 203085_s_at TGFB1 transforming growth factor, 7040 −1.75422 0.055437 0.22461 beta 1 200613_at AP2M1 adaptor-related protein 1173 −1.26768 0.05634 0.22461 complex 2, mu 1 subunit 212406_s_at PCMTD2 protein-L-isoaspartate (D- 55251 1.40919 0.057779 0.22461 aspartate) O-methyltransferase domain containing 2 212281_s_at TMEM97 transmembrane protein 97 27346 −1.25212 0.058007 0.22461 222113_s_at EPS15L1 epidermal growth factor 58513 −1.22321 0.058228 0.22461 receptor pathway substrate 15- like 1 41047_at C9orf16 chromosome 9 open reading 79095 −1.3784 0.058369 0.22461 frame 16 202083_s_at SEC14L1 SEC14-like 1 (S. cerevisiae) 6397 −1.60251 0.058462 0.22461 43544_at MED16 mediator complex subunit 16 10025 −1.37264 0.059358 0.22461 208398_s_at TBPL1 TBP-like 1 9519 −1.09285 0.060353 0.22461 200001_at CAPNS1 calpain, small subunit 1 826 −1.38469 0.060708 0.22461 203321_s_at ADNP2 ADNP homeobox 2 22850 −1.14224 0.060952 0.22461 214752_x_at FLNA filamin A, alpha 2316 −1.51816 0.061564 0.22461 221539_at EIF4EBP1 eukaryotic translation initiation 1978 −1.09846 0.062496 0.22461 factor 4E binding protein 1 208860_s_at ATRX alpha thalassemia/mental 546 1.305128 0.06313 0.22461 retardation syndrome X-linked 215933_s_at HHEX hematopoietically expressed 3087 1.399528 0.063251 0.22461 homeobox 214753_at N4BP2L2 NEDD4 binding protein 2-like 2 10443 1.043575 0.063268 0.22461 208284_x_at GGT1 gamma-glutamyltransferase 1 2678 −1.13931 0.063281 0.22461 203163_at KATNB1 katanin p80 (WD repeat 10300 −1.04468 0.06434 0.22461 containing) subunit B 1 209301_at CA2 carbonic anhydrase II 760 −1.80993 0.064349 0.22461 204480_s_at C9orf16 chromosome 9 open reading 79095 −1.50337 0.064729 0.22461 frame 16 205668_at LY75 lymphocyte antigen 75 4065 1.143917 0.064806 0.22461 211047_x_at AP2S1 adaptor-related protein 1175 −1.1541 0.065359 0.22461 complex 2, sigma 1 subunit 201563_at SORD sorbitol dehydrogenase 6652 −1.02865 0.066229 0.225836 214246_x_at MINK1 misshapen-like kinase 1 50488 −1.37631 0.066383 0.225836 212563_at BOP1 block of proliferation 1 23246 −1.07647 0.067055 0.226454 215706_x_at ZYX zyxin 7791 −1.14429 0.067478 0.226454 215116_s_at DNM1 dynamin 1 1759 −1.02496 0.067568 0.226454 209044_x_at SF3B4 splicing factor 3b, subunit 4, 10262 −1.14403 0.069176 0.227703 49 kDa 208977_x_at TUBB4B tubulin, beta 4B class IVb 10383 −1.06783 0.069385 0.227703 203175_at RHOG ras homolog family member G 391 −1.12466 0.07026 0.227703 212739_s_at NME4 NME/NM23 nucleoside 4833 −1.18 0.070482 0.227703 diphosphate kinase 4 200734_s_at ARF3 ADP-ribosylation factor 3 377 −1.10487 0.070887 0.227703 213036_x_at ATP2A3 ATPase, Ca++ transporting, 489 −1.21253 0.07161 0.227703 ubiquitous 210428_s_at HGS hepatocyte growth factor- 9146 −1.08114 0.071709 0.227703 regulated tyrosine kinase substrate 206272_at SPHAR S-phase response (cyclin 10638 −1.37986 0.071711 0.227703 related) 200742_s_at TPP1 tripeptidyl peptidase I 1200 −1.44492 0.071977 0.227703 202944_at NAGA N-acetylgalactosaminidase, 4668 −1.0861 0.073258 0.229457 alpha- 216841_s_at SOD2 superoxide dismutase 2, 6648 −1.07023 0.073344 0.229457 mitochondrial 203414_at MMD monocyte to macrophage 23531 −1.57415 0.073626 0.229457 differentiation-associated 215438_x_at GSPT1 G1 to S phase transition 1 2935 −1.03476 0.074204 0.229457 217918_at DYNLRB1 dynein, light chain, roadblock- 83658 −1.21177 0.07474 0.229995 type 1 204628_s_at ITGB3 integrin, beta 3 (platelet 3690 −1.70942 0.076434 0.233122 glycoprotein IIIa, antigen CD61) 214450_at CTSW cathepsin W 1521 −1.09904 0.076703 0.233122 203262_s_at FAM50A family with sequence similarity 9130 −1.05318 0.077683 0.233565 50, member A 216956_s_at ITGA2B integrin, alpha 2b (platelet 3674 −2.02417 0.07797 0.233565 glycoprotein IIb of IIb/IIIa complex, antigen CD41) 201639_s_at CPSF1 cleavage and polyadenylation 29894 −1.05345 0.079365 0.234598 specific factor 1, 160 kDa 36711_at MAFF v-maf musculoaponeurotic 23764 −2.66779 0.079702 0.234598 fibrosarcoma oncogene homolog F (avian) 210910_s_at POMZP3 POM121 and ZP3 fusion 22932 −0.98043 0.080921 0.234598 206390_x_at PF4 platelet factor 4 5196 −2.17632 0.081141 0.234598 218443_s_at DAZAP1 DAZ associated protein 1 26528 −0.99013 0.081405 0.234598 201052_s_at PSMF1 proteasome (prosome, 9491 −1.17083 0.081493 0.234598 macropain) inhibitor subunit 1 (PI31) 211716_x_at ARHGDIA Rho GDP dissociation inhibitor 396 −1.05994 0.081516 0.234598 (GDI) alpha 200839_s_at CTSB cathepsin B 1508 −1.23855 0.081791 0.234598 203561_at FCGR2A Fc fragment of IgG, low 2212 −1.50392 0.082039 0.234598 affinity IIa, receptor (CD32) 218611_at IER5 immediate early response 5 51278 −1.41626 0.082127 0.234598 202619_s_at PLOD2 procollagen-lysine, 2- 5352 −1.06567 0.082911 0.234625 oxoglutarate 5-dioxygenase 2 204627_s_at ITGB3 integrin, beta 3 (platelet 3690 −2.11954 0.083412 0.234625 glycoprotein IIIa, antigen CD61) 201224_s_at SRRM1 serine/arginine repetitive 10250 −1.23842 0.08352 0.234625 matrix 1 217736_s_at EIF2AK1 eukaryotic translation initiation 27102 −1.07432 0.083557 0.234625 factor 2-alpha kinase 1 200649_at NUCB1 nucleobindin 1 4924 −1.0434 0.085339 0.23596 209555_s_at CD36 CD36 molecule 948 −1.82889 0.086873 0.23596 (thrombospondin receptor) 212520_s_at SMARCA4 SWI/SNF related, matrix 6597 −1.12786 0.086976 0.23596 associated, actin dependent regulator of chromatin, subfamily a, member 4 209367_at STXBP2 syntaxin binding protein 2 6813 −1.12693 0.087289 0.23596 53071_s_at OGFOD3 2-oxoglutarate and iron- 79701 −1.02384 0.087372 0.23596 dependent oxygenase domain containing 3 221953_s_at MMP24 matrix metallopeptidase 24 10893 −1.14292 0.087422 0.23596 (membrane-inserted) 212640_at PTPLB protein tyrosine phosphatase- 201562 1.184144 0.087703 0.23596 like (proline instead of catalytic arginine), member b 201797_s_at VARS valyl-tRNA synthetase 7407 −0.95792 0.087831 0.23596 204232_at FCER1G Fc fragment of IgE, high 2207 −1.72735 0.088324 0.236346 affinity I, receptor for; gamma polypeptide 202201_at BLVRB biliverdin reductase B (flavin 645 −1.03625 0.088981 0.236552 reductase (NADPH)) 203192_at ABCB6 ATP-binding cassette, sub- 10058 −1.03424 0.090022 0.237141 family B (MDR/TAP), member 6 221829_s_at TNPO1 transportin 1 3842 −1.16481 0.090459 0.237366 213016_at BBX bobby sox homolog 56987 −1.01796 0.091007 0.237691 (Drosophila) 207574_s_at GADD45B growth arrest and DNA- 4616 −1.53642 0.091507 0.237691 damage-inducible, beta 207134_x_at TPSB2 tryptase beta 2 64499 −1.2023 0.092025 0.237791 (gene/pseudogene) 211962_s_at ZFP36L1 ZFP36 ring finger protein-like 1 677 −1.08806 0.094727 0.239603 201412_at LRP10 low density lipoprotein 26020 −1.16907 0.095687 0.239603 receptor-related protein 10 200859_x_at FLNA filamin A, alpha 2316 −1.28906 0.09598 0.239603 201760_s_at WSB2 WD repeat and SOCS box 55884 −0.9579 0.097393 0.239603 containing 2 212256_at GALNT10 UDP-N-acetyl-alpha-D- 55568 −0.9355 0.097486 0.239603 galactosamine: polypeptide N- acetylgalactosaminyltransferase 10 (GalNAc-T10) 202411_at IFI27 interferon, alpha-inducible 3429 −1.2038 0.097807 0.239603 protein 27 209190_s_at DIAPH1 diaphanous homolog 1 1729 −1.03246 0.097812 0.239603 (Drosophila) 212886_at CCDC69 coiled-coil domain containing 26112 −1.0779 0.098162 0.239603 69 215087_at C15orf39 chromosome 15 open reading 56905 −1.19136 0.09937 0.239603 frame 39 211417_x_at GGT1 gamma-glutamyltransferase 1 2678 −0.97792 0.09942 0.239603 218039_at NUSAP1 nucleolar and spindle 51203 −1.16811 0.100201 0.239603 associated protein 1 215535_s_at AGPAT1 1-acylglycerol-3-phosphate O- 10554 −1.14266 0.10071 0.239603 acyltransferase 1 219938_s_at PSTPIP2 proline-serine-threonine 9050 −1.02201 0.100884 0.239603 phosphatase interacting protein 2 213746_s_at FLNA filamin A, alpha 2316 −1.37828 0.100915 0.239603 200611_s_at WDR1 WD repeat domain 1 9948 −1.08654 0.101143 0.239603 208615_s_at PTP4A2 protein tyrosine phosphatase 8073 −1.16457 0.101287 0.239603 type IVA, member 2 208002_s_at ACOT7 acyl-CoA thioesterase 7 11332 −0.98943 0.101855 0.239603 201280_s_at DAB2 Dab, mitogen-responsive 1601 −1.47352 0.10199 0.239603 phosphoprotein, homolog 2 (Drosophila) 217529_at ORAI2 ORAI calcium release- 80228 −0.94855 0.102013 0.239603 activated calcium modulator 2 214054_at DOK2 docking protein 2, 56 kDa 9046 −1.44148 0.102476 0.239603 222043_at CLU clusterin 1191 −1.34754 0.102489 0.239603 201059_at CTTN cortactin 2017 −1.75221 0.102546 0.239603 220239_at KLHL7 kelch-like family member 7 55975 −1.04556 0.102824 0.239603 201950_x_at CAPZB capping protein (actin filament) 832 −0.9793 0.10316 0.239603 muscle Z-line, beta 207196_s_at TNIP1 TNFAIP3 interacting protein 1 10318 −1.00708 0.103374 0.239603 211160_x_at ACTN1 actinin, alpha 1 87 −1.26927 0.103783 0.239603 209350_s_at GPS2 G protein pathway suppressor 2 2874 −1.10209 0.103921 0.239603 219667_s_at BANK1 B-cell scaffold protein with 55024 −1.00308 0.104821 0.239603 ankyrin repeats 1 210075_at MARCH2 membrane-associated ring 51257 −1.43742 0.104896 0.239603 finger (C3HC4) 2, E3 ubiquitin protein ligase 201170_s_at BHLHE40 basic helix-loop-helix family, 8553 −1.52602 0.105204 0.239603 member e40 204254_s_at VDR vitamin D (1,25- 7421 −1.04354 0.10546 0.239603 dihydroxyvitamin D3) receptor 210128_s_at LTB4R leukotriene B4 receptor 1241 −0.92553 0.105789 0.239603 221210_s_at NPL N-acetylneuraminate pyruvate 80896 −1.20989 0.105822 0.239603 lyase (dihydrodipicolinate synthase) 210512_s_at VEGFA vascular endothelial growth 7422 −1.15461 0.10674 0.240343 factor A 202499_s_at SLC2A3 solute carrier family 2 6515 −1.58321 0.106858 0.240343 (facilitated glucose transporter), member 3 201125_s_at ITGB5 integrin, beta 5 3693 −1.33107 0.107555 0.24035 206414_s_at ASAP2 ArfGAP with SH3 domain, 8853 −1.34473 0.107572 0.24035 ankyrin repeat and PH domain 2 201360_at CST3 cystatin C 1471 −1.68937 0.108964 0.242661 215047_at TRIM58 tripartite motif containing 58 25893 −0.99092 0.11023 0.243627 204493_at BID BH3 interacting domain death 637 −0.9825 0.110478 0.243627 agonist 202728_s_at LTBP1 latent transforming growth 4052 −1.27115 0.113678 0.246714 factor beta binding protein 1 209969_s_at STAT1 signal transducer and activator 6772 −1.15673 0.113691 0.246714 of transcription 1, 91 kDa 205241_at SCO2 SCO2 cytochrome c oxidase 9997 −1.4845 0.114175 0.246714 assembly protein 203017_s_at SSX2IP synovial sarcoma, X breakpoint 117178 −0.94238 0.114827 0.246714 2 interacting protein 203833_s_at TGOLN2 trans-golgi network protein 2 10618 −0.93445 0.115059 0.246714 205269_at LCP2 lymphocyte cytosolic protein 2 3937 −0.97027 0.115226 0.246714 (SH2 domain containing leukocyte protein of 76 kDa) 209522_s_at CRAT carnitine O-acetyltransferase 1384 −1.01234 0.116038 0.246714 204629_at PARVB parvin, beta 29780 −1.33625 0.116976 0.246714 200609_s_at WDR1 WD repeat domain 1 9948 −0.99605 0.11718 0.246714 203680_at PRKAR2B protein kinase, cAMP- 5577 −1.23212 0.117344 0.246714 dependent, regulatory, type II, beta 208918_s_at NADK NAD kinase 65220 −1.16887 0.119342 0.248598 213716_s_at SECTM1 secreted and transmembrane 1 6398 −1.08088 0.119767 0.248718 221269_s_at SH3BGRL3 SH3 domain binding glutamic 83442 −1.35229 0.120323 0.24911 acid-rich protein like 3 212492_s_at KDM4B lysine (K)-specific demethylase 23030 −0.91067 0.121784 0.251366 4B 209729_at GAS2L1 growth arrest-specific 2 like 1 10634 −1.27348 0.12433 0.255074 204928_s_at SLC10A3 solute carrier family 10 8273 −1.17192 0.124419 0.255074 (sodium/bile acid cotransporter family), member 3 205390_s_at ANK1 ankyrin 1, erythrocytic 286 −0.88253 0.124711 0.255074 211795_s_at FYB FYN binding protein 2533 −1.18122 0.125242 0.255154 31845_at ELF4 E74-like factor 4 (ets domain 2000 −0.94729 0.125919 0.255154 transcription factor) 212573_at ENDOD1 endonuclease domain 23052 −1.40577 0.126395 0.255154 containing 1 209560_s_at DLK1 delta-like 1 homolog 8788 −1.19672 0.126533 0.255154 (Drosophila) 201095_at DAP death-associated protein 1611 −1.11419 0.126929 0.255154 212840_at UBXN7 UBX domain protein 7 26043 −1.01058 0.127011 0.255154 221267_s_at FAM108A1 family with sequence similarity 81926 −1.01634 0.128163 0.256705 108, member A1 208074_s_at AP2S1 adaptor-related protein 1175 −0.99964 0.128569 0.256758 complex 2, sigma 1 subunit 200990_at TRIM28 tripartite motif containing 28 10155 −1.00558 0.129664 0.257321 209839_at DNM3 dynamin 3 26052 −1.34338 0.130264 0.257321 201714_at TUBG1 tubulin, gamma 1 7283 −0.88297 0.130361 0.257321 200752_s_at CAPN1 calpain 1, (mu/I) large subunit 823 −0.92096 0.131139 0.258085 220751_s_at FAXDC2 fatty acid hydroxylase domain 10826 −1.32403 0.132172 0.258731 containing 2 210357_s_at SMOX spermine oxidase 54498 −1.03467 0.132612 0.258731 218175_at CCDC92 coiled-coil domain containing 92 80212 −1.09884 0.132796 0.258731 204000_at GNB5 guanine nucleotide binding 10681 −1.19778 0.133164 0.258731 protein (G protein), beta 5 217748_at ADIPOR1 adiponectin receptor 1 51094 −0.93144 0.13362 0.258731 207389_at GP1BA glycoprotein Ib (platelet), alpha 2811 −1.24025 0.134051 0.258731 polypeptide 217992_s_at EFHD2 EF-hand domain family, 79180 −1.0245 0.134143 0.258731 member D2 200884_at CKB creatine kinase, brain 1152 −0.88314 0.13483 0.259317 206145_at RHAG Rh-associated glycoprotein 6005 −1.17935 0.13531 0.259504 220757_s_at UBXN6 UBX domain protein 6 80700 −0.88851 0.136128 0.259746 213274_s_at CTSB cathepsin B 1508 −0.90565 0.136204 0.259746 202464_s_at PFKFB3 6-phosphofructo-2- 5209 −1.06242 0.137167 0.26039 kinase/fructose-2,6- biphosphatase 3 202665_s_at WIPF1 WAS/WASL interacting 7456 −1.08477 0.13731 0.26039 protein family, member 1 206488_s_at CD36 CD36 molecule 948 −1.53958 0.138985 0.260645 (thrombospondin receptor) 212089_at LMNA lamin A/C 4000 −0.92285 0.140733 0.261597 205436_s_at H2AFX H2A histone family, member X 3014 −1.00358 0.140821 0.261597 206834_at HBD hemoglobin, delta 3045 −1.42844 0.141235 0.261597 209919_x_at GGT1 gamma-glutamyltransferase 1 2678 −0.89741 0.141427 0.261597 207741_x_at TPSAB1 tryptase alpha/beta 1 7177 −1.06406 0.142116 0.261597 31874_at GAS2L1 growth arrest-specific 2 like 1 10634 −1.54272 0.142456 0.261597 201700_at CCND3 cyclin D3 896 −0.99741 0.142709 0.261597 205683_x_at TPSAB1 tryptase alpha/beta 1 7177 −1.01525 0.142713 0.261597 201061_s_at STOM stomatin 2040 −1.01078 0.14297 0.261597 203016_s_at SSX2IP synovial sarcoma, X breakpoint 117178 −0.95396 0.143425 0.261722 2 interacting protein 220496_at CLEC1B C-type lectin domain family 1, 51266 −1.54811 0.14406 0.262175 member B 209929_s_at IKBKG inhibitor of kappa light 8517 −0.89402 0.145589 0.262942 polypeptide gene enhancer in B-cells, kinase gamma 37028_at PPP1R15A protein phosphatase 1, 23645 −1.05228 0.14582 0.262942 regulatory subunit 15A 212769_at TLE3 transducin-like enhancer of 7090 −0.90676 0.14604 0.262942 split 3 (E(sp1) homolog, Drosophila) 203581_at RAB4A RAB4A, member RAS 5867 −1.01651 0.146743 0.262942 oncogene family 213956_at CEP350 centrosomal protein 350 kDa 9857 −0.85883 0.146813 0.262942 215382_x_at TPSB2 tryptase beta 2 64499 −0.977 0.148064 0.263547 (gene/pseudogene) 201830_s_at NET1 neuroepithelial cell 10276 −0.9677 0.148301 0.263547 transforming 1 201693_s_at EGR1 early growth response 1 1958 −1.15545 0.148318 0.263547 215498_s_at MAP2K3 mitogen-activated protein 5606 −1.08177 0.149281 0.264012 kinase kinase 3 204026_s_at ZWINT ZW10 interactor, kinetochore 11130 −1.12549 0.149413 0.264012 protein 209170_s_at GPM6B glycoprotein M6B 2824 0.976338 0.14975 0.264012 221211_s_at MAP3K7CL MAP3K7 C-terminal like 56911 −1.30326 0.150281 0.264261 203045_at NINJ1 ninjurin 1 4814 −1.13628 0.15069 0.264293 210084_x_at TPSAB1 tryptase alpha/beta 1 7177 −0.99706 0.151879 0.264649 207945_s_at CSNK1D casein kinase 1, delta 1453 −0.90784 0.152234 0.264649 204158_s_at TCIRG1 T-cell, immune regulator 1, 10312 −1.17593 0.152276 0.264649 ATPase, H+ transporting, lysosomal V0 subunit A3 200766_at CTSD cathepsin D 1509 −0.93104 0.153066 0.265027 215819_s_at RHCE Rh blood group, CcEe antigens 6006 −0.9917 0.154157 0.266177 203485_at RTN1 reticulon 1 6252 −1.21235 0.154517 0.266177 215240_at ITGB3 integrin, beta 3 (platelet 3690 −1.44118 0.156 0.267603 glycoprotein IIIa, antigen CD61) 201761_at MTHFD2 methylenetetrahydrofolate 10797 −0.98494 0.156692 0.267603 dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase 201904_s_at CTDSPL CTD (carboxy-terminal 10217 −0.91323 0.156796 0.267603 domain, RNA polymerase II, polypeptide A) small phosphatase-like 201906_s_at CTDSPL CTD (carboxy-terminal 10217 −0.94383 0.156925 0.267603 domain, RNA polymerase II, polypeptide A) small phosphatase-like 203854_at CFI complement factor I 3426 0.869863 0.158526 0.268092 204925_at CTNS cystinosin, lysosomal cystine 1497 −0.97532 0.158632 0.268092 transporter 204306_s_at CD151 CD151 molecule (Raph blood 977 −0.94181 0.158669 0.268092 group) 206380_s_at CFP complement factor properdin 5199 −1.1026 0.158939 0.268092 204961_s_at NCF1 neutrophil cytosolic factor 1 653361 −1.43048 0.159385 0.268092 201810_s_at SH3BP5 SH3-domain binding protein 5 9467 −1.02141 0.159588 0.268092 (BTK-associated) 204192_at CD37 CD37 molecule 951 −1.01901 0.162409 0.270814 202082_s_at SEC14L1 SEC14-like 1 (S. cerevisiae) 6397 −0.89139 0.163106 0.271309 218009_s_at PRC1 protein regulator of cytokinesis 1 9055 −1.11022 0.16572 0.274981 218522_s_at MAP1S microtubule-associated protein 1S 55201 −0.95913 0.166988 0.275781 214369_s_at RASGRP2 RAS guanyl releasing protein 2 10235 −0.91512 0.167017 0.275781 (calcium and DAG-regulated) 218243_at RUFY1 RUN and FYVE domain 80230 −1.00705 0.168966 0.278235 containing 1 214965_at SPATA2L spermatogenesis associated 2- 124044 −0.97367 0.169324 0.278235 like 212027_at RBM25 RNA binding motif protein 25 58517 −1.0829 0.17147 0.279943 218148_at CENPT centromere protein T 80152 −0.88627 0.171898 0.279943 203234_at UPP1 uridine phosphorylase 1 7378 −1.02931 0.172377 0.279943 200661_at CTSA cathepsin A 5476 −1.40173 0.172629 0.279943 210793_s_at NUP98 nucleoporin 98 kDa 4928 −1.01125 0.173817 0.279943 215464_s_at TAX1BP3 Tax1 (human T-cell leukemia 30851 −1.07322 0.174266 0.279943 virus type I) binding protein 3 204482_at CLDN5 claudin 5 7122 −1.19654 0.174447 0.279943 204198_s_at RUNX3 runt-related transcription factor 3 864 −0.98615 0.174457 0.279943 212195_at IL6ST interleukin 6 signal transducer 3572 −0.93935 0.174626 0.279943 (gp130, oncostatin M receptor) 209304_x_at GADD45B growth arrest and DNA- 4616 −0.99482 0.174913 0.279943 damage-inducible, beta 204079_at TPST2 tyrosylprotein sulfotransferase 2 8459 −1.11621 0.177613 0.283594 206167_s_at ARHGAP6 Rho GTPase activating protein 6 395 −1.27531 0.178208 0.283875 220336_s_at GP6 glycoprotein VI (platelet) 51206 −1.06098 0.183391 0.290763 214464_at CDC42BPA CDC42 binding protein kinase 8476 −0.96701 0.186028 0.292695 alpha (DMPK-like) 213887_s_at POLR2E polymerase (RNA) II (DNA 5434 −0.91232 0.186513 0.292695 directed) polypeptide E, 25 kDa 216261_at ITGB3 integrin, beta 3 (platelet 3690 −1.19784 0.187072 0.292695 glycoprotein IIIa, antigen CD61) 213836_s_at WIPI1 WD repeat domain, 55062 −1.00273 0.187347 0.292695 phosphoinositide interacting 1 218032_at SNN stannin 8303 −1.21538 0.189158 0.293378 200931_s_at VCL vinculin 7414 −0.92232 0.190234 0.294037 220110_s_at NXF3 nuclear RNA export factor 3 56000 −0.84883 0.194112 0.298064 219998_at LGALSL lectin, galactoside-binding-like 29094 −0.88669 0.19416 0.298064 200648_s_at GLUL glutamate-ammonia ligase 2752 −0.885 0.196266 0.300615 207075_at NLRP3 NLR family, pyrin domain 114548 −1.04141 0.196978 0.300727 containing 3 202814_s_at HEXIM1 hexamethylene bis-acetamide 10614 −0.86963 0.197227 0.300727 inducible 1 211582_x_at LST1 leukocyte specific transcript 1 7940 −0.89977 0.198407 0.301846 57588_at SLC24A3 solute carrier family 24 57419 −0.8268 0.199252 0.301985 (sodium/potassium/calcium exchanger), member 3 209881_s_at LAT linker for activation of T cells 27040 −0.84958 0.199391 0.301985 213537_at HLA-DPA1 major histocompatibility 3113 −1.00128 0.200355 0.302768 complex, class II, DP alpha 1 214084_x_at NCF1C neutrophil cytosolic factor 1C 654817 −1.32671 0.201691 0.303721 pseudogene 202555_s_at MYLK myosin light chain kinase 4638 −1.35821 0.201883 0.303721 222024_s_at AKAP13 A kinase (PRKA) anchor 11214 −0.9453 0.20348 0.305445 protein 13 207522_s_at ATP2A3 ATPase, Ca++ transporting, 489 −0.86192 0.204597 0.305832 ubiquitous 202228_s_at NPTN neuroplastin 27020 −0.94477 0.204641 0.305832 204396_s_at GRK5 G protein-coupled receptor 2869 −1.18973 0.205515 0.306089 kinase 5 214073_at CTTN cortactin 2017 −1.42385 0.205717 0.306089 217764_s_at RAB31 RAB31, member RAS 11031 −1.28868 0.206889 0.306253 oncogene family 208792_s_at CLU clusterin 1191 −1.32868 0.207424 0.306253 218945_at METTL22 methyltransferase like 22 79091 −0.81822 0.207478 0.306253 209166_s_at MAN2B1 mannosidase, alpha, class 2B, 4125 −0.87235 0.207908 0.306253 member 1 221856_s_at FAM63A family with sequence similarity 55793 −0.90737 0.208242 0.306253 63, member A 200622_x_at CALM3 calmodulin 3 (phosphorylase 808 −1.05371 0.208541 0.306253 kinase, delta) 216834_at RGS1 regulator of G-protein signaling 1 5996 −1.58039 0.209603 0.307146 201234_at ILK integrin-linked kinase 3611 −0.893 0.210231 0.307401 212016_s_at PTBP1 polypyrimidine tract binding 5725 −0.82271 0.214043 0.311628 protein 1 203196_at ABCC4 ATP-binding cassette, sub- 10257 −0.94809 0.215339 0.312842 family C (CFTR/MRP), member 4 204838_s_at MLH3 mutL homolog 3 (E. coli) 27030 −1.17819 0.217494 0.314178 210314_x_at TNFSF13 tumor necrosis factor (ligand) 8741 −0.85424 0.217651 0.314178 superfamily, member 13 221027_s_at PLA2G12A phospholipase A2, group XIIA 81579 −1.0047 0.219833 0.31622 207206_s_at ALOX12 arachidonate 12-lipoxygenase 239 −1.20411 0.221481 0.316376 336_at TBXA2R thromboxane A2 receptor 6915 −0.9854 0.221852 0.316376 208924_at RNF11 ring finger protein 11 26994 −0.85227 0.222362 0.316376 204440_at CD83 CD83 molecule 9308 −0.86406 0.222738 0.316376 216033_s_at FYN FYN oncogene related to SRC, 2534 −0.86181 0.222912 0.316376 FGR, YES 207414_s_at PCSK6 proprotein convertase 5046 −1.24651 0.224243 0.317072 subtilisin/kexin type 6 202014_at PPP1R15A protein phosphatase 1, 23645 −0.9299 0.224339 0.317072 regulatory subunit 15A 204256_at ELOVL6 ELOVL fatty acid elongase 6 79071 −0.916 0.225463 0.317997 216474_x_at TPSB2 tryptase beta 2 64499 −0.84525 0.227141 0.319076 (gene/pseudogene) 200696_s_at GSN gelsolin 2934 −0.94992 0.227466 0.319076 206632_s_at APOBEC3B apolipoprotein B mRNA 9582 −1.04605 0.228843 0.320097 editing enzyme, catalytic polypeptide-like 3B 221496_s_at TOB2 transducer of ERBB2, 2 10766 −0.78204 0.231572 0.323245 219630_at PDZK1IP1 PDZK1 interacting protein 1 10158 −1.15529 0.234788 0.326336 214696_at MIR22HG MIR22 host gene (non-protein 84981 −0.82752 0.235232 0.326336 coding) 213275_x_at CTSB cathepsin B 1508 −0.98223 0.235914 0.326614 215343_at CCDC88C coiled-coil domain containing 440193 −0.83997 0.23881 0.328606 88C 205347_s_at TMSB15A thymosin beta 15a 11013 −0.82645 0.241173 0.329982 213093_at PRKCA protein kinase C, alpha 5578 −0.92248 0.241407 0.329982 218217_at SCPEP1 serine carboxypeptidase 1 59342 −0.82069 0.2415 0.329982 201490_s_at PPIF peptidylprolyl isomerase F 10105 −0.81917 0.242498 0.329982 204187_at GMPR guanosine monophosphate 2766 −0.83239 0.248436 0.336382 reductase 217762_s_at RAB31 RAB31, member RAS 11031 −1.02517 0.252078 0.339954 oncogene family 204790_at SMAD7 SMAD family member 7 4092 −0.76543 0.253693 0.341452 209813_x_at TARP TCR gamma alternate reading 445347 −0.85554 0.256336 0.344324 frame protein 212636_at QKI QKI, KH domain containing, 9444 −0.79642 0.257784 0.344583 RNA binding 211429_s_at SERPINA1 serpin peptidase inhibitor, clade 5265 −1.37823 0.258343 0.344583 A (alpha-1 antiproteinase, antitrypsin), member 1 205253_at PBX1 pre-B-cell leukemia homeobox 1 5087 −0.76555 0.258565 0.344583 201735_s_at CLCN3 chloride channel, voltage- 1182 −0.94043 0.260503 0.346484 sensitive 3 205950_s_at CA1 carbonic anhydrase I 759 −0.96583 0.262137 0.347974 201334_s_at ARHGEF12 Rho guanine nucleotide 23365 −0.77329 0.264462 0.350312 exchange factor (GEF) 12 210987_x_at TPM1 tropomyosin 1 (alpha) 7168 −0.82871 0.265224 0.350312 209806_at HIST1H2BK histone cluster 1, H2bk 85236 −0.86055 0.266486 0.350312 215492_x_at PTCRA pre T-cell antigen receptor 171558 −0.904 0.271153 0.355069 alpha 205099_s_at CCR1 chemokine (C-C motif) 1230 −0.80241 0.275833 0.359113 receptor 1 202007_at NID1 nidogen 1 4811 −0.78832 0.278249 0.361563 210845_s_at PLAUR plasminogen activator, 5329 −0.82653 0.280926 0.364343 urokinase receptor 218662_s_at NCAPG non-SMC condensin I 64151 −0.73805 0.281927 0.364942 complex, subunit G 209459_s_at ABAT 4-aminobutyrate 18 −0.83695 0.28286 0.365451 aminotransferase 208161_s_at ABCC3 ATP-binding cassette, sub- 8714 −0.87352 0.283451 0.365517 family C (CFTR/MRP), member 3 210429_at RHD Rh blood group, D antigen 6007 −1.02292 0.285289 0.365856 208791_at CLU clusterin 1191 −1.10749 0.285331 0.365856 36566_at CTNS cystinosin, lysosomal cystine 1497 −0.72179 0.285335 0.365856 transporter 218711_s_at SDPR serum deprivation response 8436 −0.86687 0.285908 0.365897 201732_s_at CLCN3 chloride channel, voltage- 1182 −0.82971 0.287865 0.367365 sensitive 3 212570_at ENDOD1 endonuclease domain 23052 −0.73257 0.289756 0.368708 containing 1 203411_s_at LMNA lamin A/C 4000 −0.7781 0.290282 0.368708 211252_x_at PTCRA pre T-cell antigen receptor 171558 −0.8545 0.291611 0.369032 alpha 204908_s_at BCL3 B-cell CLL/lymphoma 3 602 −0.87358 0.292902 0.369953 218935_at EHD3 EH-domain containing 3 30845 −0.93363 0.293563 0.370097 219983_at HRASLS HRAS-like suppressor 57110 −0.72599 0.298402 0.374935 220091_at SLC2A6 solute carrier family 2 11182 −0.7439 0.298508 0.374935 (facilitated glucose transporter), member 6 212657_s_at IL1RN interleukin 1 receptor 3557 −0.78633 0.300604 0.376172 antagonist 210240_s_at CDKN2D cyclin-dependent kinase 1032 −0.7304 0.304949 0.380904 inhibitor 2D (p19, inhibits CDK4) 213338_at TMEM158 transmembrane protein 158 25907 −0.83724 0.308131 0.382561 (gene/pseudogene) 218559_s_at MAFB v-maf musculoaponeurotic 9935 −1.05359 0.308532 0.382561 fibrosarcoma oncogene homolog B (avian) 221050_s_at GTPBP2 GTP binding protein 2 54676 −0.69663 0.308832 0.382561 201131_s_at CDH1 cadherin 1, type 1, E-cadherin 999 −0.70327 0.3091 0.382561 (epithelial) 216253_s_at PARVB parvin, beta 29780 −0.85494 0.309748 0.382663 202988_s_at RGS1 regulator of G-protein signaling 1 5996 −1.01339 0.312601 0.385484 205786_s_at ITGAM integrin, alpha M (complement 3684 −0.83414 0.314385 0.386979 component 3 receptor 3 subunit) 210757_x_at DAB2 Dab, mitogen-responsive 1601 −0.74514 0.315103 0.387159 phosphoprotein, homolog 2 (Drosophila) 212723_at JMJD6 jumonji domain containing 6 23210 −0.75129 0.319118 0.391333 211743_s_at PRG2 proteoglycan 2, bone marrow 5553 −0.78462 0.319656 0.391333 (natural killer cell activator, eosinophil granule major basic protein) 222108_at AMIGO2 adhesion molecule with Ig-like 347902 −0.67947 0.320818 0.392046 domain 2 204240_s_at SMC2 structural maintenance of 10592 −0.70057 0.322141 0.392954 chromosomes 2 217763_s_at RAB31 RAB31, member RAS 11031 −0.86003 0.327317 0.397715 oncogene family 204467_s_at SNCA synuclein, alpha (non A4 6622 −0.70464 0.327807 0.397715 component of amyloid precursor) 216063_at HBBP1 hemoglobin, beta pseudogene 1 3044 −0.94717 0.329519 0.399078 202581_at HSPA1A heat shock 70 kDa protein 1 A 3303 −0.98594 0.331291 0.40042 210169_at SEC14L5 SEC14-like 5 (S. cerevisiae) 9717 −0.74193 0.33181 0.40042 57082_at LDLRAP1 low density lipoprotein 26119 −0.8255 0.333963 0.402301 receptor adaptor protein 1 217022_s_at IGH immunoglobulin heavy locus 3492 −0.84526 0.336016 0.404055 210734_x_at MAX MYC associated factor X 4149 −0.69037 0.337578 0.405064 204099_at SMARCD3 SWI/SNF related, matrix 6604 −0.66865 0.338052 0.405064 associated, actin dependent regulator of chromatin, subfamily d, member 3 218585_s_at DTL denticleless E3 ubiquitin 51514 −0.76574 0.338678 0.405098 protein ligase homolog (Drosophila) 220968_s_at TSPAN9 tetraspanin 9 10867 −0.64905 0.342149 0.408528 204993_at GNAZ guanine nucleotide binding 2781 −0.77214 0.343386 0.409282 protein (G protein), alpha z polypeptide 210992_x_at FCGR2C Fc fragment of IgG, low 9103 −0.70674 0.344048 0.409351 affinity IIc, receptor for (CD32) (gene/pseudogene) 219412_at RAB38 RAB38, member RAS 23682 −0.70456 0.345526 0.410051 oncogene family 219892_at TM6SF1 transmembrane 6 superfamily 53346 −0.67737 0.345848 0.410051 member 1 205098_at CCR1 chemokine (C-C motif) 1230 −0.67251 0.348407 0.411654 receptor 1 206883_x_at GP9 glycoprotein IX (platelet) 2815 −0.93388 0.348416 0.411654 204546_at KIAA0513 KIAA0513 9764 −0.6776 0.354075 0.416884 211984_at CALM1 calmodulin 1 (phosphorylase 801 −0.67903 0.356016 0.418443 kinase, delta) 212681_at EPB41L3 erythrocyte membrane protein 23136 −0.74882 0.363256 0.426212 band 4.1-like 3 209586_s_at PRUNE prune homolog (Drosophila) 58497 −0.71365 0.365133 0.427673 204122_at TYROBP TYRO protein tyrosine kinase 7305 −0.98164 0.368409 0.429921 binding protein 221698_s_at CLEC7A C-type lectin domain family 7, 64581 −0.72388 0.368957 0.429921 member A 202269_x_at GBP1 guanylate binding protein 1, 2633 −0.72489 0.374443 0.434817 interferon-inducible 37965_at PARVB parvin, beta 29780 −0.73203 0.378544 0.438076 20693 7_at SPTA1 spectrin, alpha, erythrocytic 1 6708 −0.63911 0.379343 0.438252 (elliptocytosis 2) 205863_at S100A12 S100 calcium binding protein 6283 −0.76877 0.385662 0.443766 A12 206465_at ACSBG1 acyl-CoA synthetase 23205 −0.69391 0.386083 0.443766 bubblegum family member 1 208601_s_at TUBB1 tubulin, beta 1 class VI 81027 −0.7751 0.38836 0.445627 208501_at GFI1B growth factor independent 1B 8328 −0.69445 0.391518 0.44802 transcription represser 204319_s_at RGS10 regulator of G-protein signaling 10 6001 −0.66481 0.391769 0.44802 204115_at GNG11 guanine nucleotide binding 2791 −0.85973 0.396611 0.450473 protein (G protein), gamma 11 222204_s_at RRN3 RRN3 RNA polymerase I 54700 −0.6018 0.396615 0.450473 transcription factor homolog (S. cerevisiae) 204446_s_at ALOX5 arachidonate 5-lipoxygenase 240 −0.88998 0.397241 0.450473 203508_at TNFRSF1B tumor necrosis factor receptor 7133 −0.6867 0.398463 0.451103 superfamily, member 1B 203305_at F13A1 coagulation factor XIII, A1 2162 −0.84164 0.401077 0.453304 polypeptide 208438_s_at FGR Gardner-Rasheed feline 2268 −0.62594 0.406618 0.458801 sarcoma viral (v-fgr) oncogene homolog 205463_s_at PDGFA platelet-derived growth factor 5154 −0.67628 0.408281 0.459911 alpha polypeptide 202917_s_at S100A8 S100 calcium binding protein A8 6279 −1.20152 0.411847 0.463156 207156_at HIST1H2AG histone cluster 1, H2ag 8969 −0.70408 0.413233 0.463944 202833_s_at SERPINA1 serpin peptidase inhibitor, clade 5265 −0.91706 0.413994 0.46403 A (alpha-1 antiproteinase, antitrypsin), member 1 207315_at CD226 CD226 molecule 10666 −0.62666 0.418074 0.466595 204971_at CSTA cystatin A (stefin A) 1475 −0.89766 0.418207 0.466595 201954_at ARPC1B actin related protein 2/3 10095 −0.64277 0.41835 0.466595 complex, subunit 1B, 41 kDa 206254_at EGF epidermal growth factor 1950 −0.61118 0.425271 0.472756 204475_at MMP1 matrix metallopeptidase 1 4312 −0.79765 0.427481 0.474434 (interstitial collagenase) 205229_s_at COCH coagulation factor C homolog, 1690 −0.53396 0.432368 0.479072 cochlin (Limulus polyphemus) 205127_at PTGS1 prostaglandin-endoperoxide 5742 −0.54531 0.44234 0.488522 synthase 1 (prostaglandin G/H synthase and cyclooxygenase) 203087_s_at KIF2A kinesin heavy chain member 2A 3796 −0.59853 0.443634 0.488965 202953_at C1QB complement component 1, q 713 −0.82302 0.444186 0.488965 subcomponent, B chain 218656_s_at LHFP lipoma HMGIC fusion partner 10186 −0.56539 0.445989 0.489822 214511_x_at FCGR1B Fc fragment of IgG, high 2210 −0.69072 0.446411 0.489822 affinity Ib, receptor (CD64) 208406_s_at GRAP2 GRB2-related adaptor protein 2 9402 −0.68765 0.451229 0.492736 56256_at SIDT2 SID1 transmembrane family, 51092 −0.74229 0.451977 0.492736 member 2 209204_at LMO4 LIM domain only 4 8543 −0.52105 0.454155 0.494314 205612_at MMRN1 multimerin 1 22915 −0.58072 0.457551 0.496919 206116_s_at TPM1 tropomyosin 1 (alpha) 7168 −0.61863 0.458017 0.496919 204858_s_at TYMP thymidine phosphorylase 1890 −0.62323 0.459985 0.497869 204308_s_at TECPR2 tectonin beta-propeller repeat 9895 −0.56607 0.460363 0.497869 containing 2 204466_s_at SNCA synuclein, alpha (non A4 6622 −0.60596 0.461512 0.498316 component of amyloid precursor) 202270_at GBP1 guanylate binding protein 1, 2633 −0.55471 0.469505 0.505333 interferon-inducible 218223_s_at PLEKHO1 pleckstrin homology domain 51177 −0.63829 0.474253 0.509634 containing, family O member 1 206881_s_at LILRA3 leukocyte immunoglobulin-like 11026 −0.61236 0.483816 0.518375 receptor, subfamily A (without TM domain), member 3 222218_s_at PILRA paired immunoglobin-like type 29992 −0.60956 0.483919 0.518375 2 receptor alpha 213566_at RNASE6 ribonuclease, RNase A family, 6039 −0.53861 0.485481 0.519227 k6 221160_s_at CABP5 calcium binding protein 5 56344 −0.52004 0.487926 0.521019 206964_at NAT8B N-acetyltransferase 8B (GCN5- 51471 −0.52553 0.491589 0.523279 related, putative, gene/pseudogene) 206420_at IGSF6 immunoglobulin superfamily, 10261 −0.58815 0.495872 0.52701 member 6 219386_s_at SLAMF8 SLAM family member 8 56833 −0.64079 0.500574 0.531173 209949_at NCF2 neutrophil cytosolic factor 2 4688 −0.64425 0.501391 0.531207 206110_at HIST1H3H histone cluster 1, H3h 8357 −0.78197 0.502267 0.531304 210660_at LILRA1 leukocyte immunoglobulin-like 11024 −0.51819 0.518847 0.547986 receptor, subfamily A (with TM domain), member 1 203560_at GGH gamma-glutamyl hydrolase 8836 −0.53164 0.520075 0.548428 (conjugase, folylpolygammaglutamyl hydrolase) 214677_x_at CYAT1 immunoglobulin lambda light 100290481 −0.49954 0.537027 0.564546 chain-like 211985_s_at CALM1 calmodulin 1 (phosphorylase 801 −0.5249 0.539781 0.566561 kinase, delta) 200660_at S100A11 S100 calcium binding protein 6282 −0.57564 0.542655 0.568696 A11 201279_s_at DAB2 Dab, mitogen-responsive 1601 −0.47879 0.546344 0.571676 phosphoprotein, homolog 2 (Drosophila) 203585_at ZNF185 zinc finger protein 185 (LIM 7739 −0.5405 0.548693 0.573249 domain) 203140_at BCL6 B-cell CLL/lymphoma 6 604 −0.48632 0.5566 0.580552 202295_s_at CTSH cathepsin H 1512 −0.54025 0.557399 0.580552 210146_x_at LILRB2 leukocyte immunoglobulin-like 10288 −0.42185 0.572195 0.593923 receptor, subfamily B (with TM and ITIM domains), member 2 212188_at KCTD12 potassium channel 115207 −0.40898 0.572868 0.593923 tetramerisation domain containing 12 203973_s_at CEBPD CCAAT/enhancer binding 1052 −0.50468 0.574596 0.594804 protein (C/EBP), delta 204588_s_at SLC7A7 solute carrier family 7 (amino 9056 −0.52401 0.57568 0.595016 acid transporter light chain, y + L system), member 7 218232_at C1QA complement component 1, q 712 −0.45679 0.578484 0.597002 subcomponent, A chain 219159_s_at SLAMF7 SLAM family member 7 57823 −0.41122 0.581677 0.599384 209448_at HTATIP2 HIV-1 Tat interactive protein 2, 10553 −0.4519 0.584526 0.601404 30 kDa 208450_at LGALS2 lectin, galactoside-binding, 3957 −0.61288 0.591141 0.607288 soluble, 2 207857_at LILRA2 leukocyte immunoglobulin-like 11027 −0.38829 0.612701 0.626584 receptor, subfamily A (with TM domain), member 2 220088_at C5AR1 complement component 5a 728 −0.41369 0.614585 0.627563 receptor 1 204912_at IL10RA interleukin 10 receptor, alpha 3587 −0.36301 0.677582 0.688773 201005_at CD9 CD9 molecule 928 −0.46299 0.696997 0.707447 205119_s_at FPR1 formyl peptide receptor 1 2357 −0.34184 0.703731 0.713213 213831_at HLA-DQA1 major histocompatibility 3117 −0.41115 0.757666 0.766726 complex, class II, DQ alpha 1 205898_at CX3CR1 chemokine (C-X3-C motif) 1524 −0.2373 0.789441 0.797689 receptor 1 201422_at IFI30 interferon, gamma- 10437 −0.26145 0.793548 0.800643 inducible protein 30 208579_x_at H2BFS H2B histone family, 54145 −0.20818 0.82651 0.83266 member S (pseudogene) 212192_at KCTD12 potassium channel 115207 −0.19775 0.828056 0.832977 tetramerisation domain containing 12 219505_at CECR1 cat eye syndrome 51816 −0.18017 0.84442 0.848178 chromosome region, candidate 1 215071_s_at HIST1H2AC histone cluster 1, 8334 −0.16128 0.864886 0.867448 H2ac

TABLE 6 Clinical Features of the Polycythemia Vera Patients Segregated by Unsupervised Hierarchical Clustering Clinical Phenotype Aggressive Indolent p Gender (M/F) 4/3 4/8 Age (median, years) 66 67.5 ns (range) (48-74) (46-82) Disease duration 16 6 0.040*  (median, years) (range) (7-28) (1-25) JAK2 V617F 100 85 ns Neutrophil Allele Burden (median, %) (range) (64-100) (55-100) Hemoglobin 11.1 13.3 0.007*  (median, gm %) (range) (8.3-12.9) (10.7-15.9) Leukocyte count 17,620 17,870 ns (median, 10³/μL) (range) (10,020-171,190) (4,430-27,270) Platelet count 454,000 837,000 ns (median, 10³/μL) (range) (171,000-1,017,000) (151,000-1,480,000) Thrombosis (n) 4/7 1/12 0.037** Palpable 7/7 6/12 0.034** splenomegaly (n) Spleen size (median, 20 2 0.005** cm below costal margin) (range) (5-32) (0-14) Splenectomy (n) 4/7 0/12 0.007** Chemotherapy (n) 5/7 2/12 0.029** Transformation to 4/7 1/12 0.037** acute leukemia (n) Surviving (n) 1/7 11/12 0.001** *Student t test **Fisher exact probability test

TABLE 7 Annotation of the 102 Concordantly Deregulated Genes Symbol (Na32 GeneID Probe consensus Gene Title (Na32 (consensus1 Adjusted set ID Mar13) consensus Mar13) Mar-13) Log2(FC) P-Value p-Value 202627_s_at SERPINE1 serpin peptidase inhibitor, 5054 1.668478 0.005041 0.454117 clade E (nexin, plasminogen activator inhibitor type 1), member 1 201324_at EMP1 epithelial membrane protein 1 2012 1.16186 0.00771 0.454117 212667_at SPARC secreted protein, acidic, 6678 1.45459 0.014744 0.454117 cysteine-rich (osteonectin) 201438_at COL6A3 collagen, type VI, alpha 3 1293 1.278559 0.025847 0.454117 211161_s_at COL3A1 collagen, type III, alpha 1 1281 1.254327 0.029648 0.454117 215076_s_at COL3A1 collagen, type III, alpha 1 1281 1.488017 0.029998 0.454117 210809_s_at POSTN periostin, osteoblast specific 10631 1.804584 0.035776 0.454117 factor 212464_s_at FN1 fibronectin 1 2335 1.813392 0.036784 0.454117 202404_s_at COL1A2 collagen, type III, alpha 1 1281 1.791759 0.037999 0.454117 202403_s_at COL1A2 collagen, type III, alpha 1 1281 1.442683 0.042962 0.454117 211719_x_at FN1 fibronectin 1 2335 1.960598 0.043407 0.454117 216442_x_at FN1 fibronectin 1 2335 1.658895 0.047165 0.454117 210495_x_at FN1 fibronectin 1 2335 1.692178 0.047228 0.454117 211964_at COL4A2 collagen, type IV, alpha 2 1284 1.078275 0.053744 0.46673 202310_s_at COL1A1 collagen, type I, alpha 1 1277 1.496322 0.056008 0.46673 217388_s_at KYNU kynureninase 8942 −1.22118 0.072655 0.470938 217232_x_at HBB hemoglobin, beta 3043 −1.35066 0.073386 0.470938 205547_s_at TAGLN transgelin 6876 1.275409 0.075803 0.470938 204848_x_at HBG1 /// hemoglobin, gamma A 3047 −1.4219 0.077286 0.470938 HBG2 211980_at COL4A1 collagen, type IV, alpha 1 1282 1.083935 0.081985 0.470938 209116_x_at HBB hemoglobin, beta 3043 −1.47367 0.087602 0.470938 213515_x_at HBG1 /// hemoglobin, gamma A 3047 −1.72304 0.089471 0.470938 HBG2 201842_s_at EFEMP1 EGF containing fibulin-like 2202 1.153114 0.09001 0.470938 extracellular matrix protein 1 204897_at PTGER4 prostaglandin E receptor 4 5734 0.979697 0.094157 0.470938 (subtype EP4) 209183_s_at C10orf10 chromosome 10 open 11067 0.631696 0.094188 0.470938 reading frame 10 204419_x_at HBG1 /// hemoglobin, gamma A 3047 −1.4151 0.105888 0.509076 HBG2 211696_x_at HBB hemoglobin, beta 3043 −1.18995 0.11201 0.513618 204141_at TUBB2A tubulin, beta 2A class IIa 7280 1.288228 0.115961 0.513618 211699_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.21697 0.122356 0.513618 HBA2 209458_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.38137 0.130596 0.513618 HBA2 221760_at MAN1A1 mannosidase, alpha, class 4121 0.85605 0.130744 0.513618 1A, member 1 204018_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.23966 0.131486 0.513618 HBA2 213350_at RPS11 ribosomal protein S11 6205 0.933771 0.136499 0.515634 215772_x_at SUCLG2 succinate-CoA ligase, GDP- 8801 −0.64738 0.145938 0.515634 forming, beta subunit 217414_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.27841 0.149825 0.515634 HBA2 205382_s_at CFD complement factor D 1675 −0.8048 0.157142 0.515634 (adipsin) 201890_at RRM2 ribonucleotide reductase M2 6241 −0.95289 0.158408 0.515634 208960_s_at KLF6 Kruppel-like factor 6 1316 0.571081 0.15952 0.515634 206157_at PTX3 pentraxin 3, long 5806 0.825089 0.160878 0.515634 205237_at FCN1 ficolin (collagen/fibrinogen 2219 −1.15146 0.170172 0.516857 domain containing) 1 204834_at FGL2 fibrinogen-like 2 10875 −0.90858 0.17194 0.516857 211745_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.33507 0.173664 0.516857 HBA2 209803_s_at PHLDA2 pleckstrin homology-like 7262 0.879169 0.180046 0.520921 domain, family A, member 2 200629_at WARS tryptophanyl-tRNA 7453 −0.69785 0.183988 0.520921 synthetase 219602_s_at PIEZO2 piezo-type 63895 −0.56733 0.187531 0.520921 mechanosensitive ion channel component 2 205848_at GAS2 growth arrest-specific 2 2620 −0.77375 0.196517 0.527987 210487_at DNTT deoxynucleotidyltransferase, 1791 0.622562 0.198523 0.527987 terminal 214414_x_at HBA1 /// hemoglobin, alpha 1 3039 −1.40997 0.215516 0.561241 HBA2 209374_s_at IGHM immunoglobulin heavy 3507 0.614952 0.226098 0.576781 constant mu 201110_s_at THBS1 thrombospondin 1 7057 0.617073 0.251014 0.58604 220377_at KIAA0125 KIAA0125 9834 0.553273 0.25106 0.58604 213524_s_at G0S2 G0/G1 switch 2 50486 −0.85706 0.265596 0.58604 204304_s_at PROM1 prominin 1 8842 0.705885 0.270019 0.58604 208961_s_at KLF6 Kruppel-like factor 6 1316 0.50248 0.272895 0.58604 203787_at SSBP2 single-stranded DNA 23635 0.483855 0.27435 0.58604 binding protein 2 212952_at LOC100507328 hypothetical 100507328 0.637258 0.276535 0.58604 LOC100507328 209763_at CHRDL1 chordin-like 1 91851 0.393371 0.278706 0.58604 202600_s_at NRIP1 nuclear receptor interacting 8204 0.586587 0.279182 0.58604 protein 1 209290_s_at NFIB nuclear factor I/B 4781 −0.55308 0.280861 0.58604 214041_x_at RPL37A ribosomal protein L37a 6168 0.490226 0.283497 0.58604 202237_at NNMT nicotinamide N- 4837 0.748218 0.285987 0.58604 methyltransferase 211074_at FOLR1 folate receptor 1 (adult) 2348 0.905935 0.306067 0.617071 204872_at TLE4 transducin-like enhancer of 7091 0.422998 0.331335 0.65741 split 4 (E(sp1) homolog, Drosophila) 217683_at HBE1 hemoglobin, epsilon 1 3046 −0.47414 0.366576 0.687129 205933_at SETBP1 SET binding protein 1 26040 0.325978 0.36816 0.687129 204430_s_at SLC2A5 solute carrier family 2 6518 0.430164 0.378886 0.687129 (facilitated glucose/fructose transporter), member 5 209894_at LEPR leptin receptor 3953 −0.51789 0.379001 0.687129 221556_at CDC14B cell division cycle 14B 8555 0.488325 0.379135 0.687129 202870_s_at CDC20 cell division cycle 20 991 −0.50504 0.379295 0.687129 204755_x_at HLF hepatic leukemia factor 3131 0.315735 0.425921 0.750089 209576_at GNAI1 guanine nucleotide binding 2770 0.312521 0.442731 0.750089 protein (G protein), alpha inhibiting activity polypeptide 1 204030_s_at IQCJ-SCHIP1 IQCJ-SCHIP1 readthrough 100505385 0.349599 0.447391 0.750089 213979_s_at — — — 0.43757 0.448237 0.750089 203535_at S100A9 S100 calcium binding 6280 −0.55271 0.46106 0.750089 protein A9 216248_s_at NR4A2 nuclear receptor subfamily 4929 −0.44972 0.465048 0.750089 4, group A, member 2 211597_s_at HOPX HOP homeobox 84525 0.403732 0.466948 0.750089 204622_x_at NR4A2 nuclear receptor subfamily 4929 −0.37372 0.468699 0.750089 4, group A, member 2 220990_s_at MIR21 microRNA 21 406991 0.336172 0.469644 0.750089 213668_s_at SOX4 SRY (sex determining 6659 0.449329 0.474056 0.750089 region Y)-box 4 205984_at CRHBP corticotropin releasing 1393 0.377363 0.518506 0.807842 hormone binding protein 209773_s_at RRM2 ribonucleotide reductase M2 6241 −0.42832 0.528182 0.807842 201058_s_at MYL9 myosin, light chain 9, 10398 0.492397 0.538149 0.807842 regulatory 201631_s_at IER3 immediate early response 3 8870 0.438819 0.542829 0.807842 219777_at GIMAP6 GTPase, IMAP family 474344 0.266496 0.54879 0.807842 member 6 212077_at CALD1 caldesmon 1 800 0.443992 0.549332 0.807842 210873_x_at APOBEC3A apolipoprotein B mRNA 200315 −0.3463 0.599089 0.852599 editing enzyme, catalytic polypeptide-like 3A 201669_s_at MARCKS myristoylated alanine-rich 4082 −0.26494 0.60049 0.852599 protein kinase C substrate 206478_at KIAA0125 KIAA0125 9834 0.32879 0.609726 0.852599 201666_at TIMP1 TIMP metallopeptidase 7076 0.267758 0.619744 0.852599 inhibitor 1 219304_s_at PDGFD platelet derived growth 80310 0.204115 0.624045 0.852599 factor D 212531_at LCN2 lipocalin 2 3934 0.323764 0.624556 0.852599 212589_at RRAS2 related RAS viral (r-ras) 22800 −0.24032 0.62995 0.852599 oncogene homolog 2 206698_at XK X-linked Kx blood group 7504 −0.27856 0.634334 0.852599 (McLeod syndrome) 209069_s_at H3F3B H3 histone, family 3B 3021 0.19436 0.64152 0.853085 (H3.3B) 213593_s_at TRA2A transformer 2 alpha 29896 0.256365 0.650412 0.855806 homolog (Drosophila) 222044_at PCIF1 PDX1 C-terminal inhibiting 63935 0.1951 0.667828 0.861405 factor 1 201798_s_at MYOF myoferlin 26509 0.273459 0.66845 0.861405 201369_s_at ZFP36L2 ZFP36 ring finger protein- 678 0.230642 0.684623 0.869074 like 2 211998_at H3F3B H3 histone, family 3B 3021 0.193469 0.693161 0.869074 (H3.3B) 214974_x_at CXCL5 chemokine (C-X-C motif) 6374 −0.26165 0.695259 0.869074 ligand 5 200999_s_at CKAP4 cytoskeleton-associated 10970 0.213798 0.708966 0.876694 protein 4 208180_s_at HIST1H4H histone cluster 1, H4h 8365 0.215184 0.725551 0.876694 214651_s_at HOXA9 homeobox A9 3205 0.201432 0.727565 0.876694 204563_at SELL selectin L 6402 0.218847 0.72941 0.876694 74694_s_at RABEP2 rabaptin, RAB GTPase 79874 0.156251 0.74234 0.879603 binding effector protein 2 209112_at CDKN1B cyclin-dependent kinase 1027 −0.16341 0.746336 0.879603 inhibitor 1B (p27, Kip1) 220416_at ATP8B4 ATPase, class I, type 8B, 79895 0.16502 0.75294 0.879603 member 4 1405_i_at CCL5 chemokine (C-C motif) 6352 −0.25823 0.790224 0.895478 ligand 5 201195_s_at SLC7A5 solute carrier family 7 8140 −0.13019 0.797734 0.895478 (amino acid transporter light chain, L system), member 5 205442_at MFAP3L microfibrillar-associated 9848 0.165446 0.798221 0.895478 protein 3-like 214911_s_at BRD2 bromodomain containing 2 6046 0.126061 0.802554 0.895478 203395_s_at HES1 hairy and enhancer of split 3280 −0.15322 0.808284 0.895478 1, (Drosophila) 213757_at EIF5A eukaryotic translation 1984 0.139559 0.810552 0.895478 initiation factor 5A 204655_at CCL5 chemokine (C-C motif) 6352 −0.23378 0.816676 0.895478 ligand 5 208892_s_at DUSP6 dual specificity phosphatase 6 1848 0.125339 0.839353 0.91234 214805_at EIF4A1 eukaryotic translation 1973 0.086848 0.847057 0.912777 initiation factor 4A1 208835_s_at LUC7L3 LUC7-like 3 (S. cerevisiae) 51747 0.092821 0.854388 0.912807 205114_s_at CCL3 /// chemokine (C-C motif) 414062 0.116024 0.882607 0.934965 CCL3L1 /// ligand 3-like 3 CCL3L3 219922_s_at LTBP3 latent transforming growth 4054 −0.06412 0.893898 0.936218 factor beta binding protein 3 207815_at PF4V1 platelet factor 4 variant 1 5197 −0.10475 0.898769 0.936218 208949_s_at LGALS3 lectin, galactoside-binding, 3958 −0.06541 0.917534 0.941056 soluble, 3 203394_s_at HES1 hairy and enhancer of split 3280 −0.06134 0.922933 0.941056 1, (Drosophila) 204753_s_at HLF hepatic leukemia factor 3131 0.037675 0.933009 0.941056 219410_at TMEM45A transmembrane protein 45A 55076 0.044462 0.933528 0.941056 219403_s_at HPSE heparanase 10855 −0.01752 0.978683 0.978683

TABLE 8 Genes Differently Regulated in the Indolent Group as Compared to the Controls Symbol Entrez (Na32 GeneID consensus Gene Title (Na32 consensus (consensus Adjusted ProbesetID Mar13) Mar13) Mar-13) Log2(FC) P-Value P-Value 208949_s_at LGALS3 lectin, galactoside-binding, soluble, 3 3958 −2.46116 4.71E−07 0.000871 202284_s_at CDKN1A cyclin-dependent kinase inhibitor 1026 −1.98698 2.11E−06 0.002134 1A (p21, Cip1) 201059_at CTTN cortactin 2017 −2.72585 6.06E−06 0.002867 211458_s_at GABARAPL1 GABA(A) receptor-associated 23710 −1.79927 1.03E−05 0.003369 protein like 1 210592_s_at SAT1 spermidine/spermine N1- 6303 −1.22693 1.17E−05 0.003384 acetyltransferase 1 201666_at TIMP1 TIMP metallopeptidase inhibitor 1 7076 −1.63942 2.35E−05 0.004281 203045_at NINJ1 ninjurin 1 4814 −1.5136 2.55E−05 0.004462 203455_s_at SAT1 spermidine/spermine N1- 6303 −1.25184 2.78E−05 0.004519 acetyltransferase 1 202912_at ADM adrenomedullin 133 −1.55855 3.02E−05 0.004672 201058_s_at MYL9 myosin, light chain 9, regulatory 10398 −2.74637 3.07E−05 0.004672 207815_at PF4V1 platelet factor 4 variant 1 5197 −2.82239 5.35E−05 0.005828 1405_i_at CCL5 chemokine (C-C motif) ligand 5 6352 −3.32637 5.85E−05 0.006036 214211_at FTH1 ferritin, heavy polypeptide 1 2495 −1.47129 8.74E−05 0.006826 201422_at IFI30 interferon, gamma-inducible 10437 −2.1056 0.000104 0.00745 protein 30 210845_s_at PLAUR plasminogen activator, urokinase 5329 −1.48981 0.000116 0.007613 receptor 214020_x_at ITGB5 integrin, beta 5 3693 −1.08903 0.000121 0.007815 204115_at GNG11 guanine nucleotide binding protein 2791 −2.43614 0.000123 0.007906 (G protein), gamma 11 213524_s_at G0S2 G0/G1 switch 2 50486 −2.65615 0.000126 0.007998 201125_s_at ITGB5 integrin, beta 5 3693 −1.67473 0.000134 0.008224 209154_at TAX1BP3 Tax1 (human T-cell leukemia virus 30851 −1.71214 0.000155 0.008862 type I) binding protein 3 201631_s_at IER3 immediate early response 3 8870 −2.29781 0.000169 0.009257 213988_s_at SAT1 spermidine/spermine N1- 6303 −1.26095 0.000171 0.009309 acetyltransferase 1 200871_s_at PSAP prosaposin 5660 −1.0306 0.000195 0.009761 200661_at CTSA cathepsin A 5476 −1.96591 0.000218 0.010227 204440_at CD83 CD83 molecule 9308 −1.34989 0.000228 0.010503 214073_at CTTN cortactin 2017 −2.15431 0.000231 0.010534 204655_at CCL5 chemokine (C-C motif) ligand 5 6352 −3.23424 0.000234 0.010534 219622_at RAB20 RAB20, member RAS oncogene 55647 −1.10241 0.000283 0.011722 family 204546_at KIAA0513 KIAA0513 9764 −1.19275 0.000321 0.012541 209304_x_at GADD45B growth arrest and DNA-damage- 4616 −1.51931 0.000364 0.013369 inducible, beta 203535_at S100A9 S100 calcium binding protein A9 6280 −2.4352 0.00037 0.013372 210075_at MARCH2 membrane-associated ring finger 51257 −1.72415 0.00043 0.014432 (C3HC4) 2, E3 ubiquitin protein ligase 213716_s_at SECTM1 secreted and transmembrane 1 6398 −1.05168 0.000482 0.015364 209398_at HIST1H1C histone cluster 1, H1c 3006 −1.53845 0.000487 0.015374 214246_x_at MINK1 misshapen-like kinase 1 50488 −1.16871 0.000487 0.015374 204482_at CLDN5 claudin 5 7122 −1.62602 0.000494 0.015531 206110_at HIST1H3H histone cluster 1, H3h 8357 −2.52014 0.000496 0.015566 200736_s_at GPX1 glutathione peroxidase 1 2876 −1.14943 0.000508 0.015789 31874_at GAS2L1 growth arrest-specific 2 like 1 10634 −1.87076 0.00052 0.016031 217764_s_at RAB31 RAB31, member RAS oncogene 11031 −2.01066 0.000564 0.016422 family AFFX- STAT1 signal transducer and activator of 6772 −1.37938 0.000621 0.016996 HUMISGF3A/ transcription 1, 91 kDa M97935_MA_at 212501_at CEBPB CCAAT/enhancer binding protein 1051 −1.54731 0.000671 0.017573 (C/EBP), beta 212077_at CALD1 caldesmon 1 800 −2.04255 0.000688 0.017825 201108_s_at THBS1 thrombospondin 1 7057 −2.12731 0.000718 0.018258 212647_at RRAS related RAS viral (r-ras) oncogene 6237 −1.08906 0.000785 0.019036 homolog 205463_s_at PDGFA platelet-derived growth factor 5154 −1.5857 0.000872 0.020261 alpha polypeptide 202083_s_at SEC14L1 SEC14-like 1 (S. cerevisiae) 6397 −1.38339 0.000926 0.020823 221211_s_at MAP3K7CL MAP3K7 C-terminal like 56911 −1.90471 0.000937 0.020912 221059_s_at COTL1 coactosin-like 1 (Dictyostelium) 23406 −1.53392 0.000965 0.021237 201743_at CD14 CD14 molecule 929 −2.10963 0.00106 0.022456 218999_at TMEM140 transmembrane protein 140 55281 −1.58682 0.001078 0.022646 218032_at SNN stannin 8303 −1.79738 0.001083 0.022694 201739_at SGK1 serum/glucocorticoid regulated 6446 −2.23217 0.001109 0.02284 kinase 1 203234_at UPP1 uridine phosphorylase 1 7378 −1.24029 0.001155 0.023122 215071_s_at HIST1H2AC histone cluster 1, H2ac 8334 −2.0219 0.001169 0.02321 202497_x_at SLC2A3 solute carrier family 2 (facilitated 6515 −1.11253 0.001169 0.02321 glucose transporter), member 3 207574_s_at GADD45B growth arrest and DNA-damage- 4616 −1.91282 0.001288 0.024289 inducible, beta AFFX- STAT1 signal transducer and activator of 6772 −1.22837 0.001313 0.024575 HUMISGF3A/ transcription 1, 91 kDa M97935_MB_at 203414_at MMD monocyte to macrophage 23531 −1.96502 0.001341 0.024732 differentiation-associated 204081_at NRGN neurogranin (protein kinase C 4900 −2.55869 0.001354 0.024788 substrate, RC3) 212242_at TUBA4A tubulin, alpha 4a 7277 −1.98963 0.001384 0.025003 211600_at PTPRO protein tyrosine phosphatase, 5800 −1.25519 0.001385 0.025003 receptor type, O 211252_x_at PTCRA pre T-cell antigen receptor alpha 171558 −1.20925 0.001454 0.025618 210357_s_at SMOX spermine oxidase 54498 −1.0824 0.00148 0.025958 214696_at MIR22HG MIR22 host gene (non-protein 84981 −1.24889 0.001532 0.026408 coding) 201506_at TGFBI transforming growth factor, beta- 7045 −1.47238 0.001571 0.026812 induced, 68 kDa 215464_s_at TAX1BP3 Tax1 (human T-cell leukemia virus 30851 −1.19481 0.001588 0.026937 type I) binding protein 3 203585_at ZNF185 zinc finger protein 185 (LIM 7739 −1.63846 0.001619 0.027302 domain) 214752_x_at FLNA filamin A, alpha 2316 −1.19726 0.001669 0.027658 216261_at ITGB3 integrin, beta 3 (platelet 3690 −1.42557 0.001715 0.028036 glycoprotein IIIa, antigen CD61) 209729_at GAS2L1 growth arrest-specific 2 like 1 10634 −1.29217 0.001761 0.02833 217763_s_at RAB31 RAB31, member RAS oncogene 11031 −1.57464 0.001927 0.029492 family 201565_s_at ID2 inhibitor of DNA binding 2, 3398 −2.05847 0.001931 0.029494 dominant negative helix-loop-helix protein 202499_s_at SLC2A3 solute carrier family 2 (facilitated 6515 −1.76034 0.001995 0.030069 glucose transporter), member 3 200859_x_at FLNA filamin A, alpha 2316 −1.14829 0.001998 0.030073 214054_at DOK2 docking protein 2, 56 kDa 9046 −1.44762 0.002111 0.030716 209959_at NR4A3 nuclear receptor subfamily 4, 8013 −1.06248 0.002113 0.030716 group A, member 3 222043_at CLU clusterin 1191 −1.24582 0.002133 0.030796 204057_at IRF8 interferon regulatory factor 8 3394 −1.20508 0.002179 0.031039 210873_x_at APOBEC3A apolipoprotein B mRNA editing 200315 −1.7692 0.002336 0.032102 enzyme, catalytic polypeptide-like 3A 204794_at DUSP2 dual specificity phosphatase 2 1844 −1.69252 0.002377 0.032376 204232_at FCER1G Fc fragment of IgE, high affinity I, 2207 −1.80094 0.002409 0.032561 receptor for; gamma polypeptide 208792_s_at CLU clusterin 1191 −1.89367 0.002436 0.032794 207414_s_at PCSK6 proprotein convertase 5046 −1.66589 0.00258 0.034033 subtilisin/kexin type 6 202295_s_at CTSH cathepsin H 1512 −1.47757 0.002604 0.034228 208078_s_at SIK1 salt-inducible kinase 1 150094 −1.38923 0.002612 0.034234 204446_s_at ALOX5 arachidonate 5-lipoxygenase 240 −1.78576 0.002664 0.034597 205863_at S100A12 S100 calcium binding protein A12 6283 −1.44064 0.002691 0.034786 212531_at LCN2 lipocalin 2 3934 −1.74945 0.002916 0.036334 204698_at ISG20 interferon stimulated exonuclease 3669 −1.01523 0.003089 0.037574 gene 20 kDa 213338_at TMEM158 transmembrane protein 158 25907 −1.19059 0.00326 0.038684 (gene/pseudogene) 215492_x_at PTCRA pre T-cell antigen receptor alpha 171558 −1.15689 0.003318 0.038883 204838_s_at MLH3 mutL homolog 3 (E. coli) 27030 −1.4825 0.00334 0.039 336_at TBXA2R thromboxane A2 receptor 6915 −1.13899 0.003359 0.039168 203140_at BCL6 B-cell CLL/lymphoma 6 604 −1.30948 0.003569 0.040549 220751_s_at FAXDC2 fatty acid hydroxylase domain 10826 −1.36 0.003658 0.041081 containing 2 205495_s_at GNLY granulysin 10578 −1.10567 0.003705 0.041271 200660_at S100A11 S100 calcium binding protein A11 6282 −1.62087 0.003733 0.041423 211429_s_at SERPINA1 serpin peptidase inhibitor, clade A 5265 −1.9862 0.003781 0.041543 (alpha-1 antiproteinase, antitrypsin), member 1 202917_s_at S100A8 S100 calcium binding protein A8 6279 −2.98812 0.003874 0.041998 205114_s_at CCL3L3 chemokine (C-C motif) ligand 3- 414062 −2.11268 0.003894 0.041998 like 3 212509_s_at MXRA7 matrix-remodeling associated 7 439921 −1.13262 0.003902 0.042016 204627_s_at ITGB3 integrin, beta 3 (platelet 3690 −2.30401 0.003953 0.042268 glycoprotein IIIa, antigen CD61) 203922_s_at CYBB cytochrome b-245, beta 1536 −1.0925 0.004058 0.043079 polypeptide 208180_s_at HIST1H4H histone cluster 1, H4h 8365 −1.58615 0.004083 0.043185 205237_at FCN1 ficolin (collagen/fibrinogen 2219 −2.31794 0.004143 0.043449 domain containing) 1 204628_s_at ITGB3 integrin, beta 3 (platelet 3690 −1.63546 0.004208 0.043687 glycoprotein IIIa, antigen CD61) 201810_s_at SH3BP5 SH3-domain binding protein 5 9467 −1.35593 0.004294 0.044285 (BTK-associated) 204621_s_at NR4A2 nuclear receptor subfamily 4, 4929 −1.13205 0.004407 0.044874 group A, member 2 214414_x_at HBA1 hemoglobin, alpha 1 3039 −2.92562 0.004429 0.044949 203305_at F13A1 coagulation factor XIII, A1 2162 −2.17585 0.004493 0.045292 polypeptide 209803_s_at PHLDA2 pleckstrin homology-like domain, 7262 −1.71861 0.00466 0.046283 family A, member 2 208161_s_at ABCC3 ATP-binding cassette, sub-family 8714 −1.21045 0.004758 0.046709 C (CFTR/MRP), member 3 208406_s_at GRAP2 GRB2-related adaptor protein 2 9402 −1.26529 0.004845 0.047046 209806_at HIST1H2BK histone cluster 1, H2bk 85236 −1.21587 0.004905 0.047465 217028_at CXCR4 chemokine (C-X-C motif) receptor 4 7852 −1.25222 0.005221 0.04911 218454_at PLBD1 phospholipase B domain 79887 −1.3316 0.005298 0.049397 containing 1 202833_s_at SERPINA1 serpin peptidase inhibitor, clade A 5265 −1.72053 0.005347 0.049661 (alpha-1 antiproteinase, antitrypsin), member 1 205220_at HCAR3 hydroxycarboxylic acid receptor 3 8843 −1.11127 0.005534 0.050489 201438_at COL6A3 collagen, type VI, alpha 3 1293 −1.45596 0.005536 0.050489 221731_x_at VCAN versican 1462 −2.02316 0.005573 0.050668 201360_at CST3 cystatin C 1471 −1.47347 0.005761 0.051649 AFFX- STAT1 signal transducer and activator of 6772 −1.22821 0.005786 0.051736 HUMISGF3A/ transcription 1, 91 kDa M97935_5_at 204858_s_at TYMP thymidine phosphorylase 1890 −1.19053 0.005857 0.052078 205547_s_at TAGLN transgelin 6876 −1.89687 0.006205 0.053812 208791_at CLU clusterin 1191 −1.6535 0.006231 0.053824 209383_at DDIT3 DNA-damage-inducible transcript 3 1649 −1.19919 0.00626 0.053842 217022_s_at IGH immunoglobulin heavy locus 3492 −1.26043 0.006498 0.054967 201280_s_at DAB2 Dab, mitogen-responsive 1601 −1.35685 0.006817 0.056659 phosphoprotein, homolog 2 (Drosophila) AFFX- — — −1.10207 0.007018 0.057621 DapX-M_at 211074_at FOLR1 folate receptor 1 (adult) 2348 −2.335 0.007106 0.057921 221556_at CDC14B cell division cycle 14B 8555 −1.35463 0.007226 0.058222 212723_at JMJD6 jumonji domain containing 6 23210 −1.10344 0.007325 0.058511 211745_x_at HBA1 hemoglobin, alpha 1 3039 −2.39195 0.007372 0.058683 204141_at TUBB2A tubulin, beta 2A class IIa 7280 −2.1393 0.007748 0.060237 208579_x_at H2BFS H2B histone family, member S 54145 −1.4314 0.008655 0.063919 (pseudogene) 203973_s_at CEBPD CCAAT/enhancer binding protein 1052 −1.24524 0.008766 0.064315 (C/EBP), delta 201170_s_at BHLHE40 basic helix-loop-helix family, 8553 −1.48301 0.008896 0.064843 member e40 205119_s_at FPR1 formyl peptide receptor 1 2357 −1.27582 0.009081 0.065557 204961_s_at NCF1 neutrophil cytosolic factor 1 653361 −1.3618 0.009093 0.06559 201616_s_at CALD1 caldesmon 1 800 −1.10576 0.009118 0.065687 204018_x_at HBA1 hemoglobin, alpha 1 3039 −1.98013 0.009214 0.066107 213539_at CD3D CD3d molecule, delta (CD3-TCR 915 −1.04108 0.009761 0.067714 complex) 202388_at RGS2 regulator of G-protein signaling 2, 5997 −1.46404 0.009794 0.06779 24 kDa 201798_s_at MYOF myoferlin 26509 −1.51466 0.009894 0.068217 203708_at PDE4B phosphodiesterase 4B, cAMP- 5142 −1.38481 0.01 0.068731 specific 214084_x_at NCF1C neutrophil cytosolic factor 1C 654817 −1.39567 0.010409 0.070394 pseudogene 209458_x_at HBA1 hemoglobin, alpha 1 3039 −2.13257 0.010802 0.071832 217762_s_at RAB31 RAB31, member RAS oncogene 11031 −1.34439 0.010983 0.072433 family 208022_s_at CDC14B cell division cycle 14B 8555 −1.06029 0.011035 0.072627 204790_at SMAD7 SMAD family member 7 4092 −1.18892 0.011176 0.072876 217414_x_at HBA1 hemoglobin, alpha 1 3039 −2.04967 0.011779 0.075213 204480_s_at C9orf16 chromosome 9 open reading frame 16 79095 −1.0583 0.01178 0.075213 204908_s_at BCL3 B-cell CLL/lymphoma 3 602 −1.12158 0.011802 0.075244 206883_x_at GP9 glycoprotein IX (platelet) 2815 −1.39492 0.012283 0.076763 211964_at COL4A2 collagen, type IV, alpha 2 1284 −1.30407 0.012296 0.076763 AFFX- GAPDH glyceraldehyde-3-phosphate 2597 −1.07979 0.012327 0.076822 HUMGAPDH/ dehydrogenase M33197_5_at 202887_s_at DDIT4 DNA-damage-inducible transcript 4 54541 −1.42927 0.012333 0.076822 AFFX- GAPDH glyceraldehyde-3-phosphate 2597 −1.25641 0.012335 0.076822 HUMGAPDH/ dehydrogenase M33197_M_at 204588_s_at SLC7A7 solute carrier family 7 (amino acid 9056 −1.19903 0.012402 0.077024 transporter light chain, y + L system), member 7 206655_s_at GP1BB glycoprotein Ib (platelet), beta 2812 −2.09441 0.0128 0.078521 polypeptide 221841_s_at KLF4 Kruppel-like factor 4 (gut) 9314 −1.65198 0.012861 0.078835 212657_s_at IL1RN interleukin 1 receptor antagonist 3557 −1.14627 0.013221 0.080181 204620_s_at VCAN versican 1462 −1.51568 0.013307 0.080358 205442_at MFAP3L microfibrillar-associated protein 3- 9848 −1.52051 0.013437 0.080854 like 200665_s_at SPARC secreted protein, acidic, cysteine- 6678 −1.75861 0.01347 0.080865 rich (osteonectin) 204396_s_at GRK5 G protein-coupled receptor kinase 5 2869 −1.28375 0.013822 0.082085 202207_at ARL4C ADP-ribosylation factor-like 4C 10123 −1.06368 0.014043 0.082963 AFFX- ACTB actin, beta 60 −1.37822 0.014382 0.0839 HSAC07/ X00351_3_at 214974_x_at CXCL5 chemokine (C-X-C motif) ligand 5 6374 −1.55942 0.014408 0.083963 213275_x_at CTSB cathepsin B 1508 −1.09109 0.014496 0.084285 214677_x_at CYAT1 immunoglobulin lambda light 100290481 −1.19702 0.014517 0.084316 chain-like 218559_s_at MAFB v-maf musculoaponeurotic 9935 −1.60023 0.014906 0.085665 fibrosarcoma oncogene homolog B (avian) 208527_x_at HIST1H2BE histone cluster 1, H2be 8344 −1.0534 0.015738 0.08838 202310_s_at COL1A1 collagen, type I, alpha 1 1277 −1.87619 0.016831 0.091891 208601_s_at TUBB1 tubulin, beta 1 class VI 81027 −1.17222 0.017934 0.095324 219403_s_at HPSE heparanase 10855 −1.31934 0.018497 0.096806 200622_x_at CALM3 calmodulin 3 (phosphorylase 808 −1.04785 0.018549 0.096942 kinase, delta) 212667_at SPARC secreted protein, acidic, cysteine- 6678 −1.34731 0.018812 0.097654 rich (osteonectin) 209949_at NCF2 neutrophil cytosolic factor 2 4688 −1.34905 0.01953 0.099726 204122_at TYROBP TYRO protein tyrosine kinase 7305 −1.58727 0.019681 0.100052 binding protein 201811_x_at SH3BP5 SH3-domain binding protein 5 9467 −1.02097 0.020101 0.101165 (BTK-associated) 214469_at HIST1H2AE histone cluster 1, H2ae 3012 −1.04742 0.020232 0.101492 200999_s_at CKAP4 cytoskeleton-associated protein 4 10970 −1.1494 0.020405 0.101743 204319_s_at RGS10 regulator of G-protein signaling 10 6001 −1.05791 0.020642 0.102328 37966_at PARVB parvin, beta 29780 −1.18316 0.020871 0.102995 AFFX- STAT1 signal transducer and activator of 6772 −1.13562 0.022192 0.106109 HUMISGF3A/ transcription 1, 91 kDa M97935_3_at 208546_x_at HIST1H2BH histone cluster 1, H2bh 8345 −1.03067 0.022452 0.106776 204834_at FGL2 fibrinogen-like 2 10875 −1.4682 0.022775 0.107256 216442_x_at FN1 fibronectin 1 2335 −1.90726 0.023141 0.108166 204103_at CCL4 chemokine (C-C motif) ligand 4 6351 −1.0683 0.02465 0.111906 221269_s_at SH3BGRL3 SH3 domain binding glutamic 83442 −1.17357 0.024677 0.111906 acid-rich protein like 3 201842_s_at EFEMP1 EGF containing fibulin-like 2202 −1.50062 0.024795 0.112138 extracellular matrix protein 1 208450_at LGALS2 lectin, galactoside-binding, soluble, 2 3957 −1.55709 0.025744 0.114214 212464_s_at FN1 fibronectin 1 2335 −1.96353 0.025831 0.114387 204971_at CSTA cystatin A (stefin A) 1475 −1.4559 0.026275 0.115382 211719_x_at FN1 fibronectin 1 2335 −2.20582 0.026796 0.116477 210495_x_at FN1 fibronectin 1 2335 −1.90768 0.026965 0.116845 216248_s_at NR4A2 nuclear receptor subfamily 4, 4929 −1.17499 0.028238 0.119726 group A, member 2 204912_at IL10RA interleukin 10 receptor, alpha 3587 −1.05258 0.02903 0.121428 211699_x_at HBA1 hemoglobin, alpha 1 3039 −1.60002 0.029162 0.121623 AFFX- ACTB actin, beta 60 −1.04373 0.029941 0.123368 HSAC07/ X00351_5_at 218280_x_at HIST2H2AA4 histone cluster 2, H2aa4 723790 −1.035 0.029948 0.123368 215240_at ITGB3 integrin, beta 3 (platelet 3690 −1.18589 0.030708 0.124841 glycoprotein IIIa, antigen CD61) 219630_at PDZK1IP1 PDZK1 interacting protein 1 10158 −1.16143 0.031505 0.126922 56256_at SIDT2 SID1 transmembrane family, 51092 −1.06356 0.03192 0.127917 member 2 214146_s_at PPBP pro-platelet basic protein 5473 −2.2804 0.032189 0.128506 (chemokine (C-X-C motif) ligand 7) 217683_at HBE1 hemoglobin, epsilon 1 3046 −1.01632 0.03275 0.12959 202627_s_at SERPINE1 serpin peptidase inhibitor, clade E 5054 −1.24155 0.035257 0.134957 (nexin, plasminogen activator inhibitor type 1), member 1 218223_s_at PLEKHO1 pleckstrin homology domain 51177 −1.02949 0.035417 0.13521 containing, family O member 1 203394_s_at HES1 hairy and enhancer of split 1, 3280 −1.19137 0.036252 0.137146 (Drosophila) 214511_x_at FCGR1B Fc fragment of IgG, high affinity 2210 −1.00332 0.036916 0.1385 Ib, receptor (CD64) 211980_at COL4A1 collagen, type IV, alpha 1 1282 −1.2568 0.037235 0.139094 215076_s_at COL3A1 collagen, type III, alpha 1 1281 −1.43307 0.038584 0.141774 218723_s_at RGCC regulator of cell cycle 28984 −1.35285 0.038884 0.142295 201465_s_at JUN jun proto-oncogene 3725 −1.23554 0.039397 0.143388 206493_at ITGA2B integrin, alpha 2b (platelet 3674 −1.40259 0.040966 0.146453 glycoprotein IIb of IIb/IIIa complex, antigen CD41) 209651_at TGFB1I1 transforming growth factor beta 1 7041 −1.18925 0.043241 0.150602 induced transcript 1 202403_s_at COL1A2 collagen, type I, alpha 2 1278 −1.44055 0.046503 0.156448 213975_s_at LYZ lysozyme 4069 −1.35445 0.046533 0.156457 202391_at BASP1 brain abundant, membrane 10409 −1.21789 0.050925 0.164058 attached signal protein 1 200897_s_at PALLD palladin, cytoskeletal associated 23022 −1.19733 0.054484 0.169794 protein 207206_s_at ALOX12 arachidonate 12-lipoxygenase 239 −1.13633 0.054626 0.170045 202404_s_at COL1A2 collagen, type I, alpha 2 1278 −1.71166 0.056539 0.173313 210809_s_at POSTN periostin, osteoblast specific factor 10631 −1.70047 0.059219 0.177986 217572_at — — −1.0617 0.061496 0.181515 204351_at S100P S100 calcium binding protein P 6286 −1.10416 0.061934 0.182039 202953_at C1QB complement component 1, q 713 −1.04337 0.061996 0.182121 subcomponent, B chain 36711_at MAFF v-maf musculoaponeurotic 23764 −2.07111 0.062874 0.183657 fibrosarcoma oncogene homolog F (avian) 214290_s_at HIST2H2AA4 histone cluster 2, H2aa4 723790 −1.00017 0.063196 0.184141 220496_at CLEC1B C-type lectin domain family 1, 51266 −1.26133 0.068125 0.192398 member B 202628_s_at SERPINE1 serpin peptidase inhibitor, clade E 5054 −1.0038 0.068895 0.193543 (nexin, plasminogen activator inhibitor type 1), member 1 201852_x_at COL3A1 collagen, type III, alpha 1 1281 −1.06074 0.069846 0.19499 209210_s_at FERMT2 fermitin family member 2 10979 −1.18848 0.071118 0.197 208937_s_at ID1 inhibitor of DNA binding 1, 3397 −1.06464 0.076912 0.204982 dominant negative helix-loop-helix protein 202644_s_at TNFAIP3 tumor necrosis factor, alpha- 7128 −1.11193 0.077731 0.206126 induced protein 3 202555_s_at MYLK myosin light chain kinase 4638 −1.20646 0.078352 0.206861 207808_s_at PROS1 protein S (alpha) 5627 −1.05757 0.080762 0.210082 202237_at NNMT nicotinamide N-methyltransferase 4837 −1.16906 0.084988 0.216541 204959_at MNDA myeloid cell nuclear differentiation 4332 −1.11553 0.099265 0.237052 antigen 206390_x_at PF4 platelet factor 4 5196 −1.56272 0.105914 0.246063 207076_s_at ASS1 argininosuccinate synthase 1 445 −1.01934 0.110808 0.252682 206494_s_at ITGA2B integrin, alpha 2b (platelet 3674 −1.21162 0.118492 0.262217 glycoprotein IIb of Ilb/IIIa complex, antigen CD41) 207140_at ALPI alkaline phosphatase, intestinal 248 −1.14253 0.12301 0.267727 216834_at RGS1 regulator of G-protein signaling 1 5996 −1.34806 0.15206 0.303847 202988_s_at RGS1 regulator of G-protein signaling 1 5996 −1.08916 0.188906 0.346892 213515_x_at HBG1 hemoglobin, gamma A 3047 −1.06377 0.246664 0.407885 212671_s_at HLA-DQA1 major histocompatibility complex, 3117 1.097239 0.126891 0.272796 class II, DQ alpha 1 211734_s_at FCER1A Fc fragment of IgE, high affinity I, 2205 1.009251 0.078698 0.207233 receptor for; alpha polypeptide 210982_s_at HLA-DRA major histocompatibility complex, 3122 1.194665 0.07091 0.196595 class II, DR alpha 202016_at MEST mesoderm specific transcript 4232 1.10616 0.05007 0.162642 209773_s_at RRM2 ribonucleotide reductase M2 6241 1.272153 0.049561 0.161602 202946_s_at BTBD3 BTB (POZ) domain containing 3 22903 1.045621 0.04313 0.150497 208894_at HLA-DRA major histocompatibility complex, 3122 1.34853 0.028179 0.119545 class II, DR alpha 213376_at ZBTB1 zinc finger and BTB domain 22890 1.088786 0.026552 0.116003 containing 1 206310_at SPINK2 serine peptidase inhibitor, Kazal 6691 1.055612 0.024944 0.112515 type 2 (acrosin-trypsin inhibitor) 203817_at GUCY1B3 guanylate cyclase 1, soluble, beta 3 2983 1.163996 0.024688 0.111906 209392_at ENPP2 ectonucleotide 5168 1.030545 0.023369 0.108718 pyrophosphatase/phosphodiesterase 2 216640_s_at PDIA6 protein disulfide isomerase family 10130 1.19128 0.020388 0.10174 A, member 6 212588_at PTPRC protein tyrosine phosphatase, 5788 1.226601 0.019819 0.100488 receptor type, C 209894_at LEPR leptin receptor 3953 1.184929 0.018148 0.09595 218039_at NUSAP1 nucleolar and spindle associated 51203 1.157405 0.017634 0.094469 protein 1 213129_s_at GCSHP5 glycine cleavage system protein H 100329108 1.10714 0.01585 0.088615 pseudogene 5 201577_at NME1 NME/NM23 nucleoside 4830 1.034901 0.015518 0.087753 diphosphate kinase 1 214741_at ZNF131 zinc finger protein 131 7690 1.072298 0.015265 0.086843 212498_at — — 1.007129 0.014477 0.084233 200953_s_at CCND2 cyclin D2 894 1.083456 0.014299 0.083701 207668_x_at PDIA6 protein disulfide isomerase family 10130 1.075588 0.014187 0.083288 A, member 6 208639_x_at PDIA6 protein disulfide isomerase family 10130 1.148925 0.013925 0.082576 A, member 6 212749_s_at RCHY1 ring finger and CHY zinc finger 25898 1.154346 0.013753 0.081884 domain containing 1, E3 ubiquitin protein ligase 213599_at OIP5 Opa interacting protein 5 11339 1.034915 0.013279 0.080287 218477_at TMEM14A transmembrane protein 14A 28978 1.038055 0.01243 0.077084 209160_at AKR1C3 aldo-keto reductase family 1, 8644 1.050868 0.012306 0.076764 member C3 207165_at HMMR hyaluronan-mediated motility 3161 1.12524 0.012278 0.076763 receptor (RHAMM) 200750_s_at RAN RAN, member RAS oncogene 5901 1.196145 0.012173 0.076447 family 200853_at H2AFZ H2A histone family, member Z 3015 1.133212 0.012107 0.076162 211762_s_at KPNA2 karyopherin alpha 2 (RAG cohort 3838 1.122517 0.011697 0.074903 1, importin alpha 1) 202591_s_at SSBP1 single-stranded DNA binding 6742 1.079587 0.011546 0.074317 protein 1, mitochondrial 212224_at ALDH1A1 aldehyde dehydrogenase 1 family, 216 1.532805 0.011256 0.073081 member A1 202157_s_at CELF2 CUGBP, Elav-like family member 2 10659 1.345852 0.011153 0.072851 201018_at EIF1AX eukaryotic translation initiation 1964 1.07069 0.011072 0.072653 factor 1A, X-linked 214359_s_at HSP90AB1 heat shock protein 90 kDa alpha 3326 1.611725 0.010493 0.070756 (cytosolic), class B member 1 202266_at TDP2 tyrosyl-DNA phosphodiesterase 2 51567 1.168396 0.009941 0.068453 204023_at RFC4 replication factor C (activator 1) 4, 5984 1.161476 0.009896 0.068217 37 kDa 208852_s_at CANX calnexin 821 1.147782 0.009836 0.067995 208990_s_at HNRNPH3 heterogeneous nuclear 3189 1.022691 0.009773 0.067735 ribonucleoprotein H3 (2H9) 201193_at IDH1 isocitrate dehydrogenase 1 3417 1.109705 0.009675 0.067345 (NADP+), soluble 204444_at KIF11 kinesin family member 11 3832 1.052307 0.009568 0.06712 202899_s_at SRSF3 serine/arginine-rich splicing factor 3 6428 1.121111 0.009554 0.067103 206834_at HBD hemoglobin, delta 3045 1.603183 0.009504 0.066927 213241_at PLXNC1 plexin C1 10154 1.098497 0.009355 0.066441 208783_s_at CD46 CD46 molecule, complement 4179 1.009037 0.009253 0.066184 regulatory protein 204905_s_at EEF1E1 eukaryotic translation elongation 9521 1.018486 0.009203 0.06606 factor 1 epsilon 1 203755_at BUB1B BUB1 mitotic checkpoint 701 1.106693 0.009061 0.065504 serine/threonine kinase B 201462_at SCRN1 secernin 1 9805 1.089176 0.008825 0.064512 207238_s_at PTPRC protein tyrosine phosphatase, 5788 1.002292 0.00794 0.060948 receptor type, C 202469_s_at CPSF6 cleavage and polyadenylation 11052 1.017757 0.007655 0.05992 specific factor 6, 68 kDa 218350_s_at GMNN geminin, DNA replication inhibitor 51053 1.289682 0.007592 0.059577 201653_at CNIH cornichon homolog (Drosophila) 10175 1.024747 0.007566 0.059412 210759_s_at PSMA1 proteasome (prosome, macropain) 5682 1.025107 0.007534 0.05925 subunit, alpha type, 1 218984_at PUS7 pseudouridylate synthase 7 54517 1.092719 0.007372 0.058683 homolog (S. cerevisiae) 213541_s_at ERG v-ets erythroblastosis virus E26 2078 1.268671 0.007213 0.058222 oncogene homolog (avian) 214214_s_at C1QBP complement component 1, q 708 1.081512 0.006939 0.057298 subcomponent binding protein 218883_s_at MLF1IP MLF1 interacting protein 79682 1.002951 0.006546 0.05522 204798_at MYB v-myb myeloblastosis viral 4602 1.33907 0.006372 0.054414 oncogene homolog (avian) 214710_s_at CCNB1 cyclin B1 891 1.30622 0.006365 0.05438 200892_s_at TRA2B transformer 2 beta homolog 6434 1.059953 0.006225 0.053824 (Drosophila) 201084_s_at BCLAF1 BCL2-associated transcription 9774 1.042614 0.006038 0.053075 factor 1 219306_at KIF15 kinesin family member 15 56992 1.005174 0.005933 0.052485 209180_at RABGGTB Rab geranylgeranyltransferase, 5876 1.030791 0.00587 0.05217 beta subunit 201829_at NET1 neuroepithelial cell transforming 1 10276 1.16411 0.005759 0.051649 213047_x_at SET SET nuclear oncogene 6418 1.072575 0.005512 0.05039 201241_at DDX1 DEAD (Asp-Glu-Ala-Asp) box 1653 1.20415 0.005509 0.05039 helicase 1 209728_at HLA-DRB4 major histocompatibility complex, 3126 2.396871 0.005479 0.050353 class II, DR beta 4 201890_at RRM2 ribonucleotide reductase M2 6241 1.743456 0.005295 0.049397 201477_s_at RRM1 ribonucleotide reductase M1 6240 1.259059 0.005293 0.049397 200728_at ACTR2 ARP2 actin-related protein 2 10097 1.079756 0.005255 0.049248 homolog (yeast) 212250_at MTDH metadherin 92140 1.112188 0.005254 0.049248 200996_at ACTR3 ARP3 actin-related protein 3 10096 1.167525 0.005078 0.048328 homolog (yeast) 203405_at PSMG1 proteasome (prosome, macropain) 8624 1.002781 0.005039 0.048111 assembly chaperone 1 200877_at CCT4 chaperonin containing TCP1, 10575 1.134112 0.004843 0.047046 subunit 4 (delta) 210438_x_at TROVE2 TROVE domain family, member 2 6738 1.075252 0.004643 0.046201 201417_at SOX4 SRY (sex determining region Y)- 6659 1.240673 0.004546 0.045582 box 4 201014_s_at PAICS phosphoribosylaminoimidazole 10606 1.325476 0.004523 0.045413 carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase 200064_at HSP90AB1 heat shock protein 90 kDa alpha 3326 1.128671 0.004413 0.044877 (cytosolic), class B member 1 202268_s_at NAE1 NEDD8 activating enzyme E1 8883 1.117633 0.004311 0.044378 subunit 1 211137_s_at ATP2C1 ATPase, Ca++ transporting, type 27032 1.024207 0.004133 0.04339 2C, member 1 218694_at ARMCX1 armadillo repeat containing, X- 51309 1.240431 0.004091 0.043202 linked 1 201676_x_at PSMA1 proteasome (prosome, macropain) 5682 1.034639 0.00406 0.043079 subunit, alpha type, 1 217987_at ASNSD1 asparagine synthetase domain 54529 1.242982 0.004059 0.043079 containing 1 219563_at LINC00341 long intergenic non-protein coding 79686 1.115324 0.004051 0.043037 RNA 341 201240_s_at LOC653566 signal peptidase complex subunit 2 653566 1.053758 0.004022 0.042778 homolog (S. cerevisiae) pseudogene 204146_at RAD51AP1 RAD51 associated protein 1 10635 1.156331 0.004016 0.042729 209757_s_at MYCN v-myc myelocytomatosis viral 4613 1.210293 0.003996 0.042614 related oncogene, neuroblastoma derived (avian) 209095_at DLD dihydrolipoamide dehydrogenase 1738 1.319642 0.003935 0.042191 211971_s_at LRPPRC leucine-rich pentatricopeptide 10128 1.113512 0.003889 0.041998 repeat containing 211746_x_at PSMA1 proteasome (prosome, macropain) 5682 1.018568 0.003854 0.041914 subunit, alpha type, 1 200052_s_at ILF2 interleukin enhancer binding factor 2 3608 1.0667 0.003851 0.041914 212640_at PTPLB protein tyrosine phosphatase-like 201562 1.131425 0.003826 0.041838 (proline instead of catalytic arginine), member b 200774_at FAM120A family with sequence similarity 120A 23196 1.114974 0.003738 0.04145 209318_x_at PLAGL1 pleiomorphic adenoma gene-like 1 5325 1.23893 0.003682 0.04125 201180_s_at GNAI3 guanine nucleotide binding protein 2773 1.037392 0.003621 0.040838 (G protein), alpha inhibiting activity polypeptide 3 215933_s_at HHEX hematopoietically expressed 3087 1.279779 0.003597 0.040702 homeobox 200807_s_at HSPD1 heat shock 60 kDa protein 1 3329 1.015247 0.00358 0.040641 (chaperonin) 202539_s_at HMGCR 3-hydroxy-3-methylglutaryl-CoA 3156 1.103166 0.003517 0.040158 reductase 200072_s_at HNRNPM heterogeneous nuclear 4670 1.402849 0.00349 0.040028 ribonucleoprotein M 204373_s_at CEP350 centrosomal protein 350 kDa 9857 1.185706 0.003481 0.040028 203209_at RFC5 replication factor C (activator 1) 5, 5985 1.113492 0.00338 0.039333 36.5 kDa 211935_at ARL6IP1 ADP-ribosylation factor-like 6 23204 1.159268 0.003341 0.039 interacting protein 1 203566_s_at AGL amylo-alpha-1,6-glucosidase, 4- 178 1.046125 0.003305 0.038871 alpha-glucanotransferase 201549_x_at KDM5B lysine (K)-specific demethylase 5B 10765 1.065448 0.003285 0.038786 208029_s_at LAPTM4B lysosomal protein transmembrane 55353 1.253963 0.003231 0.038501 4 beta 218585_s_at DTL denticleless E3 ubiquitin protein 51514 1.350603 0.003194 0.03822 ligase homolog (Drosophila) 212893_at ZZZ3 zinc finger, ZZ-type containing 3 26009 1.08034 0.003179 0.038151 215440_s_at BEX4 brain expressed, X-linked 4 56271 1.274266 0.00308 0.037537 200020_at TARDBP TAR DNA binding protein 23435 1.100346 0.002966 0.036705 213293_s_at TRIM22 tripartite motif containing 22 10346 1.403817 0.00295 0.036579 205612_at MMRN1 multimerin 1 22915 1.21464 0.002937 0.036484 201930_at MCM6 minichromosome maintenance 4175 1.051838 0.002935 0.036484 complex component 6 208910_s_at C1QBP complement component 1, q 708 1.40182 0.00291 0.036295 subcomponent binding protein 218870_at ARHGAP15 Rho GTPase activating protein 15 55843 1.442188 0.002874 0.036047 204236_at FLI1 Friend leukemia virus integration 1 2313 1.290793 0.002863 0.036016 211784_s_at SRSF1 serine/arginine-rich splicing factor 1 6426 1.027483 0.002853 0.035922 212215_at PREPL prolyl endopeptidase-like 9581 1.016567 0.002832 0.03582 201713_s_at RANBP2 RAN binding protein 2 5903 1.15906 0.002829 0.035812 201589_at SMC1A structural maintenance of 8243 1.429532 0.002826 0.035794 chromosomes 1A 201327_s_at CCT6A chaperonin containing TCP1, 908 1.110939 0.002792 0.035561 subunit 6A (zeta 1) 214949_at — — 1.096897 0.002708 0.034908 213222_at PLCB1 phospholipase C, beta 1 23236 1.045277 0.002634 0.03437 (phosphoinositide-specific) 205051_s_at KIT v-kit Hardy-Zuckerman 4 feline 3815 1.349599 0.002631 0.034353 sarcoma viral oncogene homolog 201652_at COPS5 COP9 constitutive 10987 1.133169 0.002622 0.034334 photomorphogenic homolog subunit 5 (Arabidopsis) 208767_s_at LAPTM4B lysosomal protein transmembrane 55353 1.125608 0.002597 0.034178 4 beta 204026_s_at ZWINT ZW10 interactor, kinetochore 11130 1.36409 0.002574 0.033989 protein 211615_s_at LRPPRC leucine-rich pentatricopeptide 10128 1.077666 0.002524 0.03353 repeat containing 206332_s_at IFI16 interferon, gamma-inducible 3428 1.04713 0.002479 0.033114 protein 16 213605_s_at — — 1.301604 0.002445 0.032816 219054_at NPR3 natriuretic peptide receptor 4883 1.079574 0.002372 0.032376 C/guanylate cyclase C (atrionatriuretic peptide receptor C) 212867_at NCOA2 nuclear receptor coactivator 2 10499 1.169646 0.002371 0.032376 208828_at POLE3 polymerase (DNA directed), 54107 1.189315 0.002289 0.031795 epsilon 3, accessory subunit 204127_at RFC3 replication factor C (activator 1) 3, 5983 1.217624 0.002267 0.031632 38 kDa 202599_s_at NRIP1 nuclear receptor interacting protein 1 8204 1.485341 0.002258 0.03152 212557_at ZNF451 zinc finger protein 451 26036 1.087217 0.002254 0.031489 210766_s_at CSE1L CSE1 chromosome segregation 1- 1434 1.038634 0.002233 0.031297 like (yeast) 211922_s_at CAT catalase 847 1.262699 0.002221 0.031297 205345_at BARD1 BRCA1 associated RING domain 1 580 1.097185 0.002218 0.031297 201197_at AMD1 adenosylmethionine decarboxylase 1 262 1.147451 0.002213 0.031264 204689_at HHEX hematopoietically expressed 3087 1.069023 0.002165 0.030957 homeobox 201624_at DARS aspartyl-tRNA synthetase 1615 1.026982 0.002159 0.030955 212766_s_at ISG20L2 interferon stimulated exonuclease 81875 1.137911 0.002146 0.030863 gene 20 kDa-like 2 201112_s_at CSE1L CSE1 chromosome segregation 1- 1434 1.11844 0.002142 0.030838 like (yeast) 212038_s_at VDAC1 voltage-dependent anion channel 1 7416 1.422303 0.002135 0.030796 211953_s_at IPO5 importin 5 3843 1.242501 0.002132 0.030796 212612_at RCOR1 REST corepressor 1 23186 1.102759 0.002126 0.030796 218715_at UTP6 UTP6, small subunit (SSU) 55813 1.287375 0.002119 0.030758 processome component, homolog (yeast) 217957_at C16orf80 chromosome 16 open reading 29105 1.235392 0.002104 0.030707 frame 80 208666_s_at ST13 suppression of tumorigenicity 13 6767 1.060002 0.00206 0.030421 (colon carcinoma) (Hsp70 interacting protein) 201054_at HNRNPA0 heterogeneous nuclear 10949 1.042824 0.002053 0.030384 ribonucleoprotein A0 208863_s_at SRSF1 serine/arginine-rich splicing factor 1 6426 1.155243 0.002024 0.03021 221942_s_at GUCY1A3 guanylate cyclase 1, soluble, alpha 3 2982 1.274671 0.002022 0.030194 203380_x_at SRSF5 serine/arginine-rich splicing factor 5 6430 1.094125 0.002013 0.030181 204439_at IFI44L interferon-induced protein 44-like 10964 1.917025 0.002005 0.030152 202119_s_at CPNE3 copine III 8895 1.240924 0.001996 0.030069 202491_s_at IKBKAP inhibitor of kappa light polypeptide 8518 1.162396 0.001995 0.030069 gene enhancer in B-cells, kinase complex-associated protein 200816_s_at PAFAH1B1 platelet-activating factor 5048 1.041005 0.001981 0.029948 acetylhydrolase 1b, regulatory subunit 1 (45 kDa) 203011_at IMPA1 inositol(myo)-1(or 4)- 3612 1.283329 0.001971 0.029877 monophosphatase 1 202613_at CTPS1 CTP synthase 1 1503 1.114581 0.001955 0.0297 206937_at SPTA1 spectrin, alpha, erythrocytic 1 6708 1.151575 0.001936 0.029531 (elliptocytosis 2) 212037_at PNN pinin, desmosome associated 5411 1.494883 0.001917 0.029474 protein 206052_s_at SLBP stem-loop binding protein 7884 1.082828 0.001906 0.029434 201013_s_at PAICS phosphoribosylaminoimidazole 10606 1.121467 0.00186 0.029062 carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase 209642_at BUB1 BUB1 mitotic checkpoint 699 1.034101 0.001808 0.028585 serine/threonine kinase 210425_x_at GOLGA8B golgin A8 family, member B 440270 1.211965 0.001808 0.028585 209861_s_at METAP2 methionyl aminopeptidase 2 10988 1.173435 0.001784 0.0285 221547_at PRPF18 PRP18 pre-mRNA processing 8559 1.010609 0.001784 0.0285 factor 18 homolog (S. cerevisiae) 203138_at HAT1 histone acetyltransferase 1 8520 1.697742 0.001772 0.028447 209630_s_at FBXW2 F-box and WD repeat domain 26190 1.00777 0.001755 0.028286 containing 2 201330_at RARS arginyl-tRNA synthetase 5917 1.048926 0.001753 0.028265 211727_s_at COX11 cytochrome c oxidase assembly 1353 1.104041 0.001747 0.028216 homolog 11 (yeast) 212287_at SUZ12 suppressor of zeste 12 homolog 23512 1.060589 0.001742 0.028189 (Drosophila) 208802_at SRP72 signal recognition particle 72 kDa 6731 1.080033 0.001713 0.028028 200978_at MDH1 malate dehydrogenase 1, NAD 4190 1.102564 0.001677 0.027682 (soluble) 203373_at SOCS2 suppressor of cytokine signaling 2 8835 1.193044 0.001676 0.027682 218263_s_at ZBED5 zinc finger, BED-type containing 5 58486 1.068226 0.001674 0.027682 202303_x_at SMARCA5 SWI/SNF related, matrix 8467 1.013631 0.001653 0.02757 associated, actin dependent regulator of chromatin, subfamily a, member 5 201472_at VBP1 von Hippel-Lindau binding protein 1 7411 1.093136 0.001639 0.027452 212825_at PAXIP1 PAX interacting (with 22976 1.152279 0.001534 0.026427 transcription-activation domain) protein 1 217993_s_at MAT2B methionine adenosyltransferase II, 27430 1.083589 0.001528 0.02639 beta 202113_s_at SNX2 sorting nexin 2 6643 1.270036 0.001506 0.02616 209330_s_at HNRNPD heterogeneous nuclear 3184 1.161084 0.001504 0.02616 ribonucleoprotein D (AU-rich element RNA binding protein 1, 37 kDa) 206958_s_at UPF3A UPF3 regulator of nonsense 65110 1.374126 0.001456 0.025618 transcripts homolog A (yeast) 201478_s_at DKC1 dyskeratosis congenita 1, dyskerin 1736 1.420645 0.00145 0.025591 210260_s_at TNFAIP8 tumor necrosis factor, alpha- 25816 1.079476 0.001424 0.025305 induced protein 8 205394_at CHEK1 checkpoint kinase 1 1111 1.025967 0.001414 0.025236 208966_x_at IFI16 interferon, gamma-inducible 3428 1.261519 0.001413 0.025236 protein 16 202227_s_at BRD8 bromodomain containing 8 10902 1.211398 0.001397 0.025152 202983_at HLTF helicase-like transcription factor 6596 1.292442 0.001395 0.025148 218966_at MYO5C myosin VC 55930 1.153543 0.001385 0.025003 208787_at MRPL3 mitochondrial ribosomal protein L3 11222 1.176304 0.001376 0.02497 203427_at ASF1A ASF1 anti-silencing function 1 25842 1.059991 0.001373 0.02497 homolog A (S. cerevisiae) 201260_s_at SYPL1 synaptophysin-like 1 6856 1.204425 0.001372 0.02497 212652_s_at SNX4 sorting nexin 4 8723 1.052201 0.001368 0.024963 217850_at GNL3 guanine nucleotide binding 26354 1.41406 0.00135 0.024754 protein-like 3 (nucleolar) 212435_at TRIM33 tripartite motif containing 33 51592 1.036739 0.001348 0.024743 210983_s_at MCM7 minichromosome maintenance 4176 1.380913 0.001341 0.024732 complex component 7 204510_at CDC7 cell division cycle 7 8317 1.373466 0.001299 0.024412 201970_s_at NASP nuclear autoantigenic sperm 4678 1.246396 0.00128 0.024202 protein (histone-binding) 214043_at PTPRD protein tyrosine phosphatase, 5789 1.253071 0.001271 0.02415 receptor type, D 209572_s_at EED embryonic ectoderm development 8726 1.058266 0.00127 0.02415 202890_at MAP7 microtubule-associated protein 7 9053 1.299804 0.001265 0.02408 201129_at SRSF7 serine/arginine-rich splicing factor 7 6432 1.119633 0.001254 0.023956 201699_at PSMC6 proteasome (prosome, macropain) 5706 1.503145 0.00122 0.023629 26S subunit, ATPase, 6 212266_s_at SRSF5 serine/arginine-rich splicing factor 5 6430 1.41576 0.001217 0.023629 206544_x_at SMARCA2 SWI/SNF related, matrix 6595 1.067396 0.001209 0.023601 associated, actin dependent regulator of chromatin, subfamily a, member 2 209049_s_at ZMYND8 zinc finger, MYND-type 23613 1.006778 0.001203 0.023563 containing 8 213313_at RABGAP1 RAB GTPase activating protein 1 23637 1.398753 0.001197 0.0235 222204_s_at RRN3 RRN3 RNA polymerase I 54700 1.07798 0.001196 0.0235 transcription factor homolog (S. cerevisiae) 203362_s_at MAD2L1 MAD2 mitotic arrest deficient-like 4085 1.334952 0.001171 0.02321 1 (yeast) 221264_s_at TARDBP TAR DNA binding protein 23435 1.148261 0.00117 0.02321 204009_s_at KRAS v-Ki-ras2 Kirsten rat sarcoma viral 3845 1.15051 0.001169 0.02321 oncogene homolog 213416_at ITGA4 integrin, alpha 4 (antigen CD49D, 3676 1.585393 0.00116 0.023183 alpha 4 subunit of VLA-4 receptor) 200993_at IPO7 importin 7 10527 1.052977 0.001144 0.023074 202911_at MSH6 mutS homolog 6 (E. coli) 2956 1.406267 0.00114 0.023016 201619_at PRDX3 peroxiredoxin 3 10935 1.166794 0.001136 0.02301 203743_s_at TDG thymine-DNA glycosylase 6996 1.30963 0.00113 0.022997 212199_at MRFAP1L1 Morf4 family associated protein 1- 114932 1.630757 0.001123 0.022952 like 1 202164_s_at CNOT8 CCR4-NOT transcription complex, 9337 1.199704 0.001118 0.022906 subunit 8 204809_at CLPX ClpX caseinolytic peptidase X 10845 1.04299 0.001099 0.02276 homolog (E. coli) 206542_s_at SMARCA2 SWI/SNF related, matrix 6595 1.42069 0.001047 0.022288 associated, actin dependent regulator of chromatin, subfamily a, member 2 203948_s_at MPO myeloperoxidase 4353 1.629289 0.001047 0.022288 200927_s_at RAB14 RAB14, member RAS oncogene 51552 1.113603 0.001045 0.022285 family 205961_s_at PSIP1 PC4 and SFRS1 interacting protein 1 11168 1.119456 0.001035 0.022115 203139_at DAPK1 death-associated protein kinase 1 1612 1.135088 0.001004 0.021669 219485_s_at PSMD10 proteasome (prosome, macropain) 5716 1.237831 0.000994 0.021584 26S subunit, non-ATPase, 10 202169_s_at AASDHPPT aminoadipate-semialdehyde 60496 1.491517 0.000983 0.021447 dehydrogenase- phosphopantetheinyl transferase 213761_at MDM1 Mdm1 nuclear protein homolog 56890 1.12881 0.000976 0.02135 (mouse) 212544_at ZNHIT3 zinc finger, HIT-type containing 3 9326 1.294137 0.000971 0.0213 201368_at ZFP36L2 ZFP36 ring finger protein-like 2 678 1.289879 0.000961 0.021237 218882_s_at WDR3 WD repeat domain 3 10885 1.059399 0.000955 0.021168 202431_s_at MYC v-myc myelocytomatosis viral 4609 1.493528 0.000946 0.02101 oncogene homolog (avian) 217828_at SLTM SAFB-like, transcription modulator 79811 1.118355 0.000938 0.020912 201111_at CSE1L CSE1 chromosome segregation 1- 1434 1.623491 0.000932 0.020833 like (yeast) 203474_at IQGAP2 IQ motif containing GTPase 10788 1.614975 0.000922 0.020814 activating protein 2 217906_at KLHDC2 kelch domain containing 2 23588 1.142864 0.00092 0.020814 203531_at CUL5 cullin 5 8065 1.096581 0.000891 0.020435 202746_at ITM2A integral membrane protein 2A 9452 1.664011 0.000885 0.020363 209421_at MSH2 mutS homolog 2, colon cancer, 4436 1.490121 0.00088 0.020343 nonpolyposis type 1 (E. coli) 213698_at ZMYM6NB ZMYM6 neighbor 100506144 1.042591 0.00087 0.020236 218605_at TFB2M transcription factor B2, 64216 1.183958 0.000854 0.02007 mitochondrial 201947_s_at CCT2 chaperonin containing TCP1, 10576 1.143067 0.000853 0.02007 subunit 2 (beta) 202602_s_at HTATSF1 HIV-1 Tat specific factor 1 27336 1.187599 0.000849 0.020015 202930_s_at SUCLA2 succinate-CoA ligase, ADP- 8803 1.176902 0.000838 0.019818 forming, beta subunit 201277_s_at HNRNPAB heterogeneous nuclear 3182 1.014906 0.000822 0.019567 ribonucleoprotein A/B 208798_x_at GOLGA8A golgin A8 family, member A 23015 1.082102 0.000821 0.019567 202413_s_at USP1 ubiquitin specific peptidase 1 7398 1.360578 0.000801 0.01926 201742_x_at SRSF1 serine/arginine-rich splicing factor 1 6426 1.198562 0.000799 0.01924 218014_at NUP85 nucleoporin 85 kDa 79902 1.180004 0.000796 0.019229 204240_s_at SMC2 structural maintenance of 10592 1.406601 0.000787 0.01907 chromosomes 2 209337_at PSIP1 PC4 and SFRS1 interacting protein 1 11168 1.241851 0.000784 0.019026 201273_s_at SRP9 signal recognition particle 9 kDa 6726 1.202073 0.000784 0.019026 222303_at — — 1.254922 0.000781 0.019002 212330_at TFDP1 transcription factor Dp-1 7027 1.341814 0.00078 0.019002 203432_at TMPO thymopoietin 7112 1.068195 0.000768 0.01881 203493_s_at CEP57 centrosomal protein 57 kDa 9702 1.03691 0.000766 0.018788 202330_s_at UNG uracil-DNA glycosylase 7374 1.326002 0.000761 0.018729 209814_at ZNF330 zinc finger protein 330 27309 1.444996 0.000758 0.018729 203560_at GGH gamma-glutamyl hydrolase 8836 1.446967 0.00075 0.018617 (conjugase, folylpolygammaglutamyl hydrolase) 209112_at CDKN1B cyclin-dependent kinase inhibitor 1027 1.181993 0.000749 0.018617 1B (p27, Kip1) 35974_at LRMP lymphoid-restricted membrane 4033 1.001783 0.000732 0.018537 protein 208643_s_at XRCC5 X-ray repair complementing 7520 1.057033 0.000731 0.018525 defective repair in Chinese hamster cells 5 (double-strand-break rejoining) 214651_s_at HOXA9 homeobox A9 3205 1.466349 0.000687 0.017825 204767_s_at FEN1 flap structure-specific 2237 1.47296 0.000685 0.017799 endonuclease 1 202658_at PEX11B peroxisomal biogenesis factor 11 8799 1.013624 0.000684 0.017799 beta 218989_x_at SLC30A5 solute carrier family 30 (zinc 64924 1.011398 0.000683 0.017799 transporter), member 5 212740_at PIK3R4 phosphoinositide-3-kinase, 30849 1.016978 0.000678 0.017687 regulatory subunit 4 212378_at GART phosphoribosylglycinamide 2618 1.210756 0.000671 0.017573 formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase 221931_s_at SEH1L SEH1-like (S. cerevisiae) 81929 1.151366 0.000671 0.017573 201830_s_at NET1 neuroepithelial cell transforming 1 10276 1.193353 0.000654 0.017314 202174_s_at PCM1 pericentriolar material 1 5108 1.195075 0.000641 0.017181 202717_s_at CDC16 cell division cycle 16 8881 1.000687 0.000632 0.017087 204720_s_at DNAJC6 DnaJ (Hsp40) homolog, subfamily 9829 1.165169 0.00063 0.017071 C, member 6 202503_s_at KIAA0101 KIAA0101 9768 1.410664 0.000627 0.01707 212513_s_at USP33 ubiquitin specific peptidase 33 23032 1.349055 0.000623 0.01703 203583_at UNC50 unc-50 homolog (C. elegans) 25972 1.021413 0.000607 0.016773 209199_s_at MEF2C myocyte enhancer factor 2C 4208 1.384786 0.000605 0.016755 203949_at MPO myeloperoxidase 4353 2.09466 0.0006 0.016728 213088_s_at DNAJC9 DnaJ (Hsp40) homolog, subfamily 23234 1.165365 0.0006 0.016728 C, member 9 201873_s_at ABCE1 ATP-binding cassette, sub-family 6059 1.123959 0.000598 0.016728 E (OABP), member 1 201518_at CBX1 chromobox homolog 1 10951 1.118253 0.000591 0.016699 221771_s_at MPHOSPH8 M-phase phosphoprotein 8 54737 1.003732 0.000588 0.016642 218236_s_at PRKD3 protein kinase D3 23683 1.039419 0.00058 0.016542 218979_at RMI1 RMI1, RecQ mediated genome 80010 1.012559 0.000577 0.016542 instability 1, homolog (S. cerevisiae) 201532_at PSMA3 proteasome (prosome, macropain) 5684 1.445319 0.000575 0.016531 subunit, alpha type, 3 212653_s_at EHBP1 EH domain binding protein 1 23301 1.032735 0.000566 0.016422 210338_s_at HSPA8 heat shock 70 kDa protein 8 3312 1.574514 0.000564 0.016422 218642_s_at CHCHD7 coiled-coil-helix-coiled-coil-helix 79145 1.029917 0.000561 0.016422 domain containing 7 221970_s_at NOL11 nucleolar protein 11 25926 1.054307 0.00056 0.016422 202741_at PRKACB protein kinase, cAMP-dependent, 5567 1.048386 0.000557 0.016422 catalytic, beta 209905_at HOXA9 homeobox A9 3205 1.24736 0.000554 0.016422 202589_at TYMS thymidylate synthetase 7298 1.65426 0.000548 0.01628 200071_at SMNDC1 survival motor neuron domain 10285 1.034914 0.000544 0.016265 containing 1 201303_at EIF4A3 eukaryotic translation initiation 9775 1.17097 0.000539 0.016206 factor 4A3 205632_s_at PIP5K1B phosphatidylinositol-4-phosphate 8395 1.175229 0.000533 0.016113 5-kinase, type I, beta 215380_s_at GGCT gamma-glutamylcyclotransferase 79017 1.189841 0.000531 0.016099 203765_at GCA grancalcin, EF-hand calcium 25801 1.046003 0.00053 0.016099 binding protein 220865_s_at PDSS1 prenyl (decaprenyl) diphosphate 23590 1.074485 0.000525 0.016054 synthase, subunit 1 202446_s_at PLSCR1 phospholipid scramblase 1 5359 1.327281 0.000524 0.01605 200970_s_at SERP1 stress-associated endoplasmic 27230 1.075633 0.000512 0.015879 reticulum protein 1 216920_s_at TARP TCR gamma alternate reading 445347 1.485156 0.000485 0.015374 frame protein 212693_at MDN1 MDN1, midasin homolog (yeast) 23195 1.087501 0.000484 0.015374 213359_at HNRNPD heterogeneous nuclear 3184 1.09076 0.000478 0.015321 ribonucleoprotein D (AU-rich element RNA binding protein 1, 37 kDa) 206102_at GINS1 GINS complex subunit 1 (Psf1 9837 1.575105 0.000474 0.015221 homolog) 202950_at CRYZ crystallin, zeta (quinone reductase) 1429 1.315997 0.000472 0.015221 202395_at NSF N-ethylmaleimide-sensitive factor 4905 1.021689 0.000471 0.015221 220615_s_at FAR2 fatty acyl CoA reductase 2 55711 1.050613 0.000469 0.015212 211700_s_at TRO trophinin 7216 1.068948 0.000465 0.015212 206095_s_at SRSF10 serine/arginine-rich splicing factor 10 10772 1.179453 0.000464 0.015212 208694_at PRKDC protein kinase, DNA-activated, 5591 1.097773 0.000458 0.015075 catalytic polypeptide 214141_x_at SRSF7 serine/arginine-rich splicing factor 7 6432 1.331333 0.000439 0.014608 203517_at MTX2 metaxin 2 10651 1.225852 0.000439 0.014608 205857_at SLC18A2 solute carrier family 18 (vesicular 6571 1.065076 0.000431 0.014432 monoamine), member 2 203856_at VRK1 vaccinia related kinase 1 7443 1.237886 0.00043 0.014432 203372_s_at SOCS2 suppressor of cytokine signaling 2 8835 1.09312 0.00042 0.014308 221652_s_at ASUN asunder, spermatogenesis regulator 55726 1.363988 0.000412 0.014181 212690_at DDHD2 DDHD domain containing 2 23259 1.236377 0.000412 0.014181 208808_s_at HMGB2 high mobility group box 2 3148 1.445021 0.000402 0.014069 212896_at SKIV2L2 superkiller viralicidic activity 2- 23517 1.098253 0.000395 0.013905 like 2 (S. cerevisiae) 221622_s_at TMEM126B transmembrane protein 126B 55863 1.103945 0.000394 0.013871 218303_x_at KRCC1 lysine-rich coiled-coil 1 51315 1.054683 0.000393 0.013857 201479_at DKC1 dyskeratosis congenita 1, dyskerin 1736 1.261576 0.00039 0.013806 203156_at AKAP11 A kinase (PRKA) anchor protein 11 11215 1.181561 0.000384 0.013683 201756_at RPA2 replication protein A2, 32 kDa 6118 1.039715 0.000379 0.013533 209903_s_at ATR ataxia telangiectasia and Rad3 545 1.074716 0.000376 0.013488 related 206976_s_at HSPH1 heat shock 105 kDa/110 kDa protein 1 10808 1.254331 0.000376 0.013488 219454_at EGFL6 EGF-like-domain, multiple 6 25975 1.30877 0.000367 0.013369 211144_x_at TARP TCR gamma alternate reading 445347 1.365625 0.000366 0.013369 frame protein 205133_s_at HSPE1 heat shock 10 kDa protein 1 3336 1.081382 0.000365 0.013369 (chaperonin 10) 202429_s_at PPP3CA protein phosphatase 3, catalytic 5530 1.056462 0.000363 0.013369 subunit, alpha isozyme 210038_at PRKCQ protein kinase C, theta 5588 1.046788 0.000358 0.013295 205668_at LY75 lymphocyte antigen 75 4065 1.075449 0.000357 0.013295 201515_s_at TSN translin 7247 1.30897 0.000349 0.01317 221825_at ANGEL2 angel homolog 2 (Drosophila) 90806 1.010739 0.000347 0.013115 212168_at RBM12 RNA binding motif protein 12 10137 1.209363 0.000346 0.013115 201555_at MCM3 minichromosome maintenance 4172 1.057831 0.000343 0.013089 complex component 3 208766_s_at HNRNPR heterogeneous nuclear 10236 1.04567 0.000341 0.013032 ribonucleoprotein R 213294_at EIF2AK2 eukaryotic translation initiation 5610 1.224521 0.000339 0.012995 factor 2-alpha kinase 2 217956_s_at ENOPH1 enolase-phosphatase 1 58478 1.13057 0.000325 0.012646 212211_at ANKRD17 ankyrin repeat domain 17 26057 1.06166 0.000321 0.012541 218396_at VPS13C vacuolar protein sorting 13 54832 1.169643 0.000315 0.012391 homolog C (S. cerevisiae) 202020_s_at LANCL1 LanC lantibiotic synthetase 10314 1.265915 0.000314 0.012374 component C-like 1 (bacterial) 213304_at FAM179B family with sequence similarity 23116 1.05681 0.000311 0.01229 179, member B 214093_s_at FUBP1 far upstream element (FUSE) 8880 1.19343 0.000311 0.01229 binding protein 1 221761_at ADSS adenylosuccinate synthase 159 1.010834 0.000308 0.012252 201386_s_at DHX15 DEAH (Asp-Glu-Ala-His) box 1665 1.650845 0.000306 0.012244 polypeptide 15 221505_at ANP32E acidic (leucine-rich) nuclear 81611 1.183054 0.000303 0.012139 phosphoprotein 32 family, member E 218127_at NFYB nuclear transcription factor Y, beta 4801 1.104339 0.00029 0.011904 219303_at RNF219 ring finger protein 219 79596 1.119496 0.000279 0.011636 218133_s_at NIF3L1 NIF3 NGG1 interacting factor 3- 60491 1.192936 0.000269 0.011358 like 1 (S. cerevisiae) 203428_s_at ASF1A ASF1 anti-silencing function 1 25842 1.128273 0.000268 0.011351 homolog A (S. cerevisiae) 219037_at RRP15 ribosomal RNA processing 15 51018 1.057006 0.000267 0.011351 homolog (S. cerevisiae) 218889_at NOC3L nucleolar complex associated 3 64318 1.366019 0.000262 0.011306 homolog (S. cerevisiae) 201413_at HSD17B4 hydroxysteroid (17-beta) 3295 1.140766 0.000255 0.011131 dehydrogenase 4 212526_at SPG20 spastic paraplegia 20 (Troyer 23111 1.026783 0.000251 0.01101 syndrome) 208021_s_at RFC1 replication factor C (activator 1) 1, 5981 1.039138 0.00025 0.010974 145 kDa 213253_at SMC2 structural maintenance of 10592 1.034612 0.000246 0.010839 chromosomes 2 218713_at NARG2 NMDA receptor regulated 2 79664 1.010022 0.000244 0.010824 209092_s_at GLOD4 glyoxalase domain containing 4 51031 1.452265 0.000233 0.010534 208634_s_at MACF1 microtubule-actin crosslinking 23499 1.053724 0.000229 0.010503 factor 1 202854_at HPRT1 hypoxanthine 3251 1.377438 0.000227 0.010458 phosphoribosyltransferase 1 202345_s_at FABP5 fatty acid binding protein 5 2171 1.412774 0.000223 0.010332 (psoriasis-associated) 217832_at SYNCRIP synaptotagmin binding, 10492 1.449861 0.000222 0.010305 cytoplasmic RNA interacting protein 220742_s_at NGLY1 N-glycanase 1 55768 1.055086 0.00022 0.010287 202318_s_at SENP6 SUMO1/sentrin specific peptidase 26054 1.021802 0.000214 0.010126 6 202892_at CDC23 cell division cycle 23 8697 1.142138 0.000212 0.010103 201964_at SETX senataxin 23064 1.253372 0.000211 0.010103 209056_s_at CDC5L cell division cycle 5-like 988 1.214199 0.000208 0.010028 214047_s_at MBD4 methyl-CpG binding domain 8930 1.011612 0.000208 0.010028 protein 4 201603_at PPP1R12A protein phosphatase 1, regulatory 4659 1.089584 0.000204 0.00993 subunit 12A 208716_s_at TMCO1 transmembrane and coiled-coil 54499 1.113356 0.000202 0.009867 domains 1 218710_at TTC27 tetratricopeptide repeat domain 27 55622 1.090229 0.000201 0.009867 216221_s_at PUM2 pumilio homolog 2 (Drosophila) 23369 1.105518 0.000201 0.009867 202107_s_at MCM2 minichromosome maintenance 4171 1.506995 0.000201 0.009867 complex component 2 214453_s_at IFI44 interferon-induced protein 44 10561 1.719005 0.0002 0.009867 208775_at XPO1 exportin 1 (CRM1 homolog, yeast) 7514 1.473631 0.000198 0.009851 211929_at HNRNPA3 heterogeneous nuclear 220988 1.257569 0.000198 0.009839 ribonucleoprotein A3 212406_s_at PCMTD2 protein-L-isoaspartate (D- 55251 1.452466 0.000196 0.009776 aspartate) O-methyltransferase domain containing 2 204354_at POT1 protection of telomeres 1 25913 1.126965 0.000194 0.009746 218323_at RHOT1 ras homolog family member T1 55288 1.007825 0.000186 0.009582 200994_at IPO7 importin 7 10527 1.001576 0.000186 0.009582 201773_at ADNP activity-dependent neuroprotector 23394 1.388566 0.000183 0.009532 homeobox 202060_at CTR9 Ctr9, Paf1/RNA polymerase II 9646 1.453326 0.00018 0.00945 complex component, homolog (S. cerevisiae) 209218_at SQLE squalene epoxidase 6713 1.758399 0.000177 0.009364 209580_s_at MBD4 methyl-CpG binding domain 8930 1.160508 0.000174 0.009336 protein 4 202633_at TOPBP1 topoisomerase (DNA) II binding 11073 1.197566 0.000173 0.009336 protein 1 213106_at ATP8A1 ATPase, aminophospholipid 10396 1.20933 0.000168 0.009246 transporter (APLT), class I, type 8A, member 1 212058_at U2SURP U2 snRNP-associated SURP 23350 1.398897 0.000168 0.009246 domain containing 212408_at TOR1AIP1 torsin A interacting protein 1 26092 1.153349 0.000163 0.009063 203067_at PDHX pyruvate dehydrogenase complex, 8050 1.024437 0.00016 0.009007 component X 202184_s_at NUP133 nucleoporin 133 kDa 55746 1.163427 0.000156 0.008893 204749_at NAP1L3 nucleosome assembly protein 1- 4675 1.756608 0.000149 0.008702 like 3 212621_at TMEM194A transmembrane protein 194A 23306 1.117235 0.000148 0.008702 200723_s_at CAPRIN1 cell cycle associated protein 1 4076 1.360735 0.000145 0.008669 219008_at C2orf43 chromosome 2 open reading frame 43 60526 1.160627 0.000144 0.008657 202220_at KIAA0907 KIAA0907 22889 1.542705 0.000144 0.008657 211987_at TOP2B topoisomerase (DNA) II beta 7155 1.023919 0.000143 0.008633 180 kDa 202441_at ERLIN1 ER lipid raft associated 1 10613 1.221226 0.000141 0.008533 218171_at VPS4B vacuolar protein sorting 4 homolog 9525 1.099892 0.000138 0.008402 B (S. cerevisiae) 209974_s_at BUB3 BUB3 mitotic checkpoint protein 9184 1.177194 0.000136 0.008296 219412_at RAB38 RAB38, member RAS oncogene 23682 1.455958 0.000133 0.008144 family 205474_at CRLF3 cytokine receptor-like factor 3 51379 1.012784 0.000132 0.008144 222201_s_at CASP8AP2 caspase 8 associated protein 2 9994 1.164562 0.00013 0.008097 208838_at CAND1 cullin-associated and neddylation- 55832 1.071114 0.000128 0.007998 dissociated 1 204521_at FAM216A family with sequence similarity 29902 1.272748 0.000124 0.007921 216, member A 213506_at F2RL1 coagulation factor II (thrombin) 2150 1.465639 0.000123 0.007906 receptor-like 1 214988_s_at SON SON DNA binding protein 6651 1.293714 0.00012 0.007803 218005_at ZNF22 zinc finger protein 22 7570 1.363822 0.000117 0.007673 202798_at SEC24B SEC24 family, member B 10427 1.217371 0.000115 0.007613 (S. cerevisiae) 203519_s_at UPF2 UPF2 regulator of nonsense 26019 1.021857 0.000114 0.007613 transcripts homolog (yeast) 213227_at PGRMC2 progesterone receptor membrane 10424 1.088092 0.000114 0.007613 component 2 212918_at RECQL RecQ protein-like (DNA helicase 5965 1.204724 0.000111 0.007613 Q1-like) 218842_at RPAP3 RNA polymerase II associated 79657 1.007012 0.000109 0.007613 protein 3 218370_s_at S100PBP S100P binding protein 64766 1.040583 0.000107 0.007601 209043_at PAPSS1 3′-phosphoadenosine 5′- 9061 1.266585 0.000106 0.007558 phosphosulfate synthase 1 213374_x_at HIBCH 3-hydroxyisobutyryl-CoA 26275 1.37257 0.000104 0.00745 hydrolase 201202_at PCNA proliferating cell nuclear antigen 5111 1.874541 0.000102 0.00739 208925_at CLDND1 claudin domain containing 1 56650 1.035219 0.000101 0.007343 208986_at TCF12 transcription factor 12 6938 1.13518 9.80E−05 0.00719 202706_s_at UMPS uridine monophosphate synthetase 7372 1.021819 9.71E−05 0.007147 222209_s_at TMEM135 transmembrane protein 135 65084 1.139737 9.39E−05 0.007017 202956_at ARFGEF1 ADP-ribosylation factor guanine 10565 1.048197 9.25E−05 0.006996 nucleotide-exchange factor 1 (brefeldin A-inhibited) 208877_at PAK2 p21 protein (Cdc42/Rac)-activated 5062 1.095691 9.02E−05 0.006891 kinase 2 212454_x_at HNRPDL heterogeneous nuclear 9987 1.012227 8.99E−05 0.006891 ribonucleoprotein D-like 201832_s_at USO1 USO1 vesicle transport factor 8615 1.196724 8.58E−05 0.006807 218104_at TEX10 testis expressed 10 54881 1.063963 8.48E−05 0.006794 209585_s_at MINPP1 multiple inositol-polyphosphate 9562 1.5483 8.34E−05 0.006749 phosphatase 1 204160_s_at ENPP4 ectonucleotide 22875 1.023317 8.15E−05 0.006724 pyrophosphatase/phosphodiesterase 4 (putative) 201872_s_at ABCE1 ATP-binding cassette, sub-family 6059 1.056302 7.77E−05 0.006497 E (OABP), member 1 203608_at ALDH5A1 aldehyde dehydrogenase 5 family, 7915 1.567849 7.76E−05 0.006497 member A1 201177_s_at UBA2 ubiquitin-like modifier activating 10054 1.011771 7.72E−05 0.006497 enzyme 2 201663_s_at SMC4 structural maintenance of 10051 1.397017 7.58E−05 0.006462 chromosomes 4 206478_at KIAA0125 KIAA0125 9834 1.699586 7.39E−05 0.006369 209259_s_at SMC3 structural maintenance of 9126 1.536331 7.36E−05 0.006369 chromosomes 3 201491_at AHSA1 AHA1, activator of heat shock 10598 1.017409 7.09E−05 0.006348 90 kDa protein ATPase homolog 1 (yeast) 200050_at ZNF146 zinc finger protein 146 7705 1.112747 6.82E−05 0.006137 212798_s_at ANKMY2 ankyrin repeat and MYND domain 57037 1.282009 6.82E−05 0.006137 containing 2 200597_at EIF3A eukaryotic translation initiation 8661 1.15333 6.58E−05 0.006137 factor 3, subunit A 220416_at ATP8B4 ATPase, class I, type 8B, member 4 79895 1.319886 6.56E−05 0.006137 218352_at RCBTB1 regulator of chromosome 55213 1.401043 6.56E−05 0.006137 condensation (RCC1) and BTB (POZ) domain containing protein 1 208954_s_at LARP4B La ribonucleoprotein domain 23185 1.035215 6.55E−05 0.006137 family, member 4B 200754_x_at SRSF2 serine/arginine-rich splicing factor 2 6427 1.189498 6.53E−05 0.006137 213094_at GPR126 G protein-coupled receptor 126 57211 1.723615 6.36E−05 0.006137 201726_at ELAVL1 ELAV (embryonic lethal, 1994 1.210067 6.33E−05 0.006137 abnormal vision, Drosophila)-like 1 (Hu antigen R) 202797_at SACM1L SAC1 suppressor of actin 22908 1.068996 6.19E−05 0.006092 mutations 1-like (yeast) 218932_at ZNHIT6 zinc finger, HIT-type containing 6 54680 1.533903 6.11E−05 0.006036 205909_at POLE2 polymerase (DNA directed), 5427 1.13581 6.10E−05 0.006036 epsilon 2, accessory subunit 201493_s_at PUM2 pumilio homolog 2 (Drosophila) 23369 1.045091 6.09E−05 0.006036 203605_at SRP54 signal recognition particle 54 kDa 6729 1.336501 6.08E−05 0.006036 213737_x_at GOLGA8H golgin A8 family, member H 728498 1.276782 5.98E−05 0.006036 205848_at GAS2 growth arrest-specific 2 2620 1.882946 5.69E−05 0.005965 207483_s_at CAND1 cullin-associated and neddylation- 55832 1.101083 5.60E−05 0.005911 dissociated 1 219497_s_at BCL11A B-cell CLL/lymphoma 11A (zinc 53335 1.051534 5.48E−05 0.00586 finger protein) 201664_at SMC4 structural maintenance of 10051 1.810802 5.39E−05 0.005828 chromosomes 4 209362_at MED21 mediator complex subunit 21 9412 1.351739 5.36E−05 0.005828 201458_s_at BUB3 BUB3 mitotic checkpoint protein 9184 1.194027 5.30E−05 0.005828 203804_s_at LUC7L3 LUC7-like 3 (S. cerevisiae) 51747 1.117694 5.28E−05 0.005828 206316_s_at KNTC1 kinetochore associated 1 9735 1.132251 5.10E−05 0.00579 204030_s_at IQCJ- IQCJ-SCHIP1 readthrough 100505385 1.123787 5.04E−05 0.005746 SCHIP1 218437_s_at LZTFL1 leucine zipper transcription factor- 54585 1.226372 4.98E−05 0.005732 like 1 202502_at ACADM acyl-CoA dehydrogenase, C-4 to 34 1.024159 4.94E−05 0.005732 C-12 straight chain 204256_at ELOVL6 ELOVL fatty acid elongase 6 79071 1.533869 4.93E−05 0.005732 215165_x_at UMPS uridine monophosphate synthetase 7372 1.104322 4.89E−05 0.005732 217814_at CCDC47 coiled-coil domain containing 47 57003 1.430862 4.63E−05 0.005622 212944_at SLC5A3 solute carrier family 5 6526 1.422266 4.48E−05 0.005619 (sodium/myo-inositol cotransporter), member 3 208861_s_at ATRX alpha thalassemia/mental 546 1.174112 4.47E−05 0.005619 retardation syndrome X-linked 208848_at ADH5 alcohol dehydrogenase 5 (class 128 1.350061 4.32E−05 0.005587 III), chi polypeptide 209813_x_at TARP TCR gamma alternate reading 445347 1.675539 4.27E−05 0.005556 frame protein 13 213005_s_at KANK1 KN motif and ankyrin repeat 23189 1.420285 2.37E−05 0.004281 domains 1 201086_x_at SON SON DNA binding protein 6651 1.303827 2.37E−05 0.004281 205885_s_at ITGA4 integrin, alpha 4 (antigen CD49D, 3676 1.152728 2.32E−05 0.004281 alpha 4 subunit of VLA-4 receptor) 218957_s_at PAAF1 proteasomal ATPase-associated 80227 1.082321 2.32E−05 0.004281 factor 1 209409_at GRB10 growth factor receptor-bound 2887 1.411903 2.31E−05 0.004281 protein 10 218428_s_at REV1 REV1, polymerase (DNA directed) 51455 1.014141 2.30E−05 0.004281 212982_at ZDHHC17 zinc finger, DHHC-type containing 17 23390 1.24448 2.23E−05 0.004281 206854_s_at MAP3K7 mitogen-activated protein kinase 6885 1.362632 2.14E−05 0.004215 kinase kinase 7 213164_at SLC5A3 solute carrier family 5 6526 1.12656 2.14E−05 0.004215 (sodium/myo-inositol cotransporter), member 3 209662_at CETN3 centrin, EF-hand protein, 3 1070 1.780447 2.13E−05 0.004215 213092_x_at DNAJC9 DnaJ (Hsp40) homolog, subfamily 23234 1.281922 2.11E−05 0.004215 C, member 9 219130_at TRMT13 tRNA methyltransferase 13 54482 1.054729 2.09E−05 0.004215 homolog (S. cerevisiae) 218096_at AGPAT5 1-acylglycerol-3-phosphate O- 55326 1.046759 2.05E−05 0.004215 acyltransferase 5 200783_s_at STMN1 stathmin 1 3925 1.021197 1.99E−05 0.004183 202763_at CASP3 caspase 3, apoptosis-related 836 1.113632 1.97E−05 0.004167 cysteine peptidase 206874_s_at SLK STE20-like kinase 9748 1.508576 1.95E−05 0.004162 215806_x_at TARP TCR gamma alternate reading 445347 1.699601 1.94E−05 0.004162 frame protein 218139_s_at AP5M1 adaptor-related protein complex 5, 55745 1.213838 1.93E−05 0.004162 mu 1 subunit 212731_at ANKRD46 ankyrin repeat domain 46 157567 1.139853 1.87E−05 0.004117 217317_s_at HERC2P2 hect domain and RLD 2 400322 1.063595 1.62E−05 0.003764 pseudogene 2 212176_at PNISR PNN-interacting serine/arginine- 25957 1.0103 1.62E−05 0.003764 rich protein 218313_s_at GALNT7 UDP-N-acetyl-alpha-D- 51809 1.507414 1.62E−05 0.003764 galactosamine:polypeptide N- acetylgalactosaminyltransferase 7 (GalNAc-T7) 219083_at SHQ1 SHQ1, H/ACA ribonucleoprotein 55164 1.675814 1.53E−05 0.003721 assembly factor 203302_at DCK deoxycytidine kinase 1633 1.276653 1.43E−05 0.003616 218515_at PAXBP1 PAX3 and PAX7 binding protein 1 94104 1.243818 1.43E−05 0.003616 213391_at DPY19L4 dpy-19-like 4 (C. elegans) 286148 1.187053 1.29E−05 0.003444 202907_s_at NBN nibrin 4683 1.588244 1.26E−05 0.003444 217886_at EPS15 epidermal growth factor receptor 2060 1.345925 1.23E−05 0.003411 pathway substrate 15 218622_at NUP37 nucleoporin 37 kDa 79023 1.261215 1.22E−05 0.003411 208654_s_at CD164 CD164 molecule, sialomucin 8763 1.456204 1.21E−05 0.003411 219035_s_at RNF34 ring finger protein 34, E3 ubiquitin 80196 1.187459 1.15E−05 0.003369 protein ligase 220044_x_at LUC7L3 LUC7-like 3 (S. cerevisiae) 51747 1.199028 1.15E−05 0.003369 218768_at NUP107 nucleoporin 107 kDa 57122 1.457543 1.14E−05 0.003369 208405_s_at CD164 CD164 molecule, sialomucin 8763 1.103873 1.11E−05 0.003369 212675_s_at CEP68 centrosomal protein 68 kDa 23177 1.33608 1.11E−05 0.003369 209200_at MEF2C myocyte enhancer factor 2C 4208 1.964319 1.10E−05 0.003369 209476_at TMX1 thioredoxin-related transmembrane 81542 1.209672 1.07E−05 0.003369 protein 1 212474_at AVL9 AVL9 homolog (S. cerevisiase) 23080 1.128401 9.17E−06 0.003236 203306_s_at SLC35A1 solute carrier family 35 (CMP- 10559 1.184632 9.10E−06 0.003236 sialic acid transporter), member A1 219405_at TRIM68 tripartite motif containing 68 55128 1.092848 8.27E−06 0.003067 217954_s_at PHF3 PHD finger protein 3 23469 1.096771 8.00E−06 0.003017 201448_at TIA1 TIA1 cytotoxic granule-associated 7072 1.364827 7.61E−06 0.002919 RNA binding protein 202918_s_at MOB4 MOB family member 4, phocein 25843 1.281577 7.60E−06 0.002919 201503_at G3BP1 GTPase activating protein (SH3 10146 1.400871 7.40E−06 0.002919 domain) binding protein 1 221606_s_at HMGN5 high mobility group nucleosome 79366 1.041186 7.16E−06 0.002919 binding domain 5 212179_at PNISR PNN-interacting serine/arginine- 25957 1.659487 7.06E−06 0.002919 rich protein 207943_x_at PLAGL1 pleiomorphic adenoma gene-like 1 5325 1.02225 6.80E−06 0.002919 219002_at FASTKD1 FAST kinase domains 1 79675 1.139996 6.78E−06 0.002919 219649_at ALG6 ALG6, alpha-1,3- 29929 1.318705 6.36E−06 0.002919 glucosyltransferase 218593_at RBM28 RNA binding motif protein 28 55131 1.095331 6.00E−06 0.002867 218152_at HMG20A high mobility group 20A 10363 1.329726 5.52E−06 0.002834 218108_at UBR7 ubiquitin protein ligase E3 55148 1.468044 4.88E−06 0.002649 component n-recognin 7 (putative) 212959_s_at GNPTAB N-acetylglucosamine-1-phosphate 79158 1.108946 4.43E−06 0.002528 transferase, alpha and beta subunits 213653_at METTL3 methyltransferase like 3 56339 1.135123 4.23E−06 0.002528 201218_at CTBP2 C-terminal binding protein 2 1488 1.622964 4.00E−06 0.002528 202520_s_at MLH1 mutL homolog 1, colon cancer, 4292 1.112927 3.95E−06 0.002528 nonpolyposis type 2 (E. coli) 209022_at STAG2 stromal antigen 2 10735 1.149995 3.82E−06 0.002528 218343_s_at GTF3C3 general transcription factor IIIC, 9330 1.144191 3.71E−06 0.002528 polypeptide 3, 102 kDa 219960_s_at UCHL5 ubiquitin carboxyl-terminal 51377 1.108112 3.64E−06 0.002528 hydrolase L5 209175_at SEC23IP SEC23 interacting protein 11196 1.255797 3.63E−06 0.002528 218170_at ISOC1 isochorismatase domain containing 1 51015 1.24304 3.49E−06 0.002528 209265_s_at METTL3 methyltransferase like 3 56339 1.227046 3.29E−06 0.002528 222127_s_at EXOC1 exocyst complex component 1 55763 1.394408 2.86E−06 0.002528 207002_s_at PLAGL1 pleiomorphic adenoma gene-like 1 5325 1.171723 2.49E−06 0.002309 204168_at MGST2 microsomal glutathione S- 4258 1.037395 1.79E−06 0.001991 transferase 2 205609_at ANGPT1 angiopoietin 1 284 1.547029 1.71E−06 0.001991 209537_at EXTL2 exostosin-like glycosyltransferase 2 2135 1.05732 7.39E−07 0.001096 209748_at SPAST spastin 6683 1.096487 6.60E−07 0.001049 218397_at FANCL Fanconi anemia, complementation 55120 1.889757 4.53E−07 0.000871 group L 210621_s_at RASA1 RAS p21 protein activator 5921 1.39113 3.67E−07 0.000871 (GTPase activating protein) 1 201687_s_at API5 apoptosis inhibitor 5 8539 1.055434 1.84E−07 0.000682 212828_at SYNJ2 synaptojanin 2 8871 1.111098 1.84E−07 0.000682 209007_s_at C1orf63 chromosome 1 open reading frame 63 57035 1.046263 8.11E−08 0.000601 218361_at GOLPH3L golgi phosphoprotein 3-like 55204 1.174016 5.59E−08 0.000601 219913_s_at CRNKL1 crooked neck pre-mRNA splicing 51340 1.468407 2.17E−08 0.000482 factor-like 1 (Drosophila)

TABLE 9 Genes Differently Regulated in the Aggressive Group as Compared to the Controls Entrez Symbol (Na32 GeneID consensus (consensus Adjusted Probeset ID Mar13) Gene Title (Na32 consensus Mar13) Mar-13) Log2 (FC) P-Value P-Value 209763_at CHRDL1 chordin-like 1 91851 −1.17606 5.21E−09 6.67E−05 210487_at DNTT deoxynucleotidyltransferase, terminal 1791 −1.91383 6.00E−09 6.67E−05 205933_at SETBP1 SET binding protein 1 26040 −1.1773 1.51E−08 0.000112 202723_s_at FOXO1 forkhead box O1 2308 −1.10201 4.34E−06 0.024108 201324_at EMP1 epithelial membrane protein 1 2012 −1.73635 6.04E−06 0.026802 201325_s_at EMP1 epithelial membrane protein 1 2012 −1.00997 1.48E−05 0.029925 209398_at HIST1H1C histone cluster 1, H1c 3006 −2.26773 3.33E−05 0.061697 212827_at IGHM immunoglobulin heavy constant mu 3507 −1.62695 0.000114 0.134692 206385_s_at ANK3 ankyrin 3, node of Ranvier (ankyrin G) 288 −1.01371 0.000117 0.134692 209183_s_at C10orf10 chromosome 10 open reading frame 10 11067 −1.07496 0.000131 0.139056 209374_s_at IGHM immunoglobulin heavy constant mu 3507 −1.78678 0.000238 0.21202 204430_s_at SLC2A5 solute carrier family 2 (facilitated 6518 −1.13053 0.00026 0.213741 glucose/fructose transporter), member 5 200872_at S100A10 S100 calcium binding protein A10 6281 −1.47658 0.000279 0.215629 209069_s_at H3F3B H3 histone, family 3B (H3.3B) 3021 −1.18661 0.000318 0.221129 210592_s_at SAT1 spermidine/spermine N1- 6303 −1.08035 0.000376 0.227751 acetyltransferase 1 207111_at EMR1 egf-like module containing, mucin-like, 2015 −1.08619 0.000401 0.227751 hormone receptor-like 1 204304_s_at PROM1 prominin 1 8842 −1.82999 0.00042 0.227751 205984_at CRHBP corticotropin releasing hormone binding 1393 −1.68559 0.000482 0.239161 protein 218280_x_at HIST2H2AA4 histone cluster 2, H2aa4 723790 −2.04755 0.000661 0.271413 211997_x_at H3F3B H3 histone, family 3B (H3.3B) 3021 −1.22595 0.000753 0.293064 211998_at H3F3B H3 histone, family 3B (H3.3B) 3021 −1.37161 0.001101 0.376554 214290_s_at HIST2H2AA4 histone cluster 2, H2aa4 723790 −2.10063 0.001825 0.399532 202888_s_at ANPEP alanyl (membrane) aminopeptidase 290 −1.09433 0.001827 0.399532 210785_s_at THEMIS2 thymocyte selection associated family 9473 −1.40909 0.001958 0.412534 member 2 205402_x_at PRSS2 protease, serine, 2 (trypsin 2) 5645 −1.05383 0.002001 0.412534 220990_s_at MIR21 microRNA 21 406991 −1.16662 0.002023 0.412534 201369_s_at ZFP36L2 ZFP36 ring finger protein-like 2 678 −1.42932 0.002729 0.450281 207571_x_at THEMIS2 thymocyte selection associated family 9473 −1.3478 0.0028 0.450281 member 2 212543_at AIM1 absent in melanoma 1 202 −1.12719 0.002817 0.450281 204698_at ISG20 interferon stimulated exonuclease gene 3669 −1.19993 0.002841 0.450281 20 kDa 204872_at TLE4 transducin-like enhancer of split 4 7091 −1.08661 0.004743 0.516178 (E(sp1) homolog, Drosophila) 211597_s_at HOPX HOP homeobox 84525 −1.35699 0.004787 0.516178 220377_at KIAA0125 KIAA0125 9834 −1.15785 0.004957 0.516178 202708_s_at HIST2H2BE histone cluster 2, H2be 8349 −1.73994 0.00501 0.516178 222258_s_at SH3BP4 SH3-domain binding protein 4 23677 −1.25738 0.006817 0.549162 202748_at GBP2 guanylate binding protein 2, interferon- 2634 −1.47788 0.007224 0.557788 inducible 222067_x_at HIST1H2BD histone cluster 1, H2bd 3017 −1.3732 0.007682 0.562835 204805_s_at H1FX H1 histone family, member X 8971 −1.45025 0.012357 0.587079 214472_at HIST1H2AD histone cluster 1, H2ad 3013 −1.33457 0.016968 0.609599 215071_s_at HIST1H2AC histone cluster 1, H2ac 8334 −1.59794 0.020339 0.631601 204057_at IRF8 interferon regulatory factor 8 3394 −1.01328 0.021285 0.631601 221760_at MAN1A1 mannosidase, alpha, class 1A, member 1 4121 −1.18372 0.02233 0.632753 208490_x_at HIST1H2BF histone cluster 1, H2bf 8343 −1.14111 0.027318 0.639545 221556_at CDC14B cell division cycle 14B 8555 −1.26289 0.028048 0.64494 210387_at HIST1H2BG histone cluster 1, H2bg 8339 −1.14146 0.02951 0.651733 201416_at SOX4 SRY (sex determining region Y)-box 4 6659 −1.05187 0.032258 0.65293 208579_x_at H2BFS H2B histone family, member S 54145 −1.30549 0.035551 0.658786 (pseudogene) 208527_x_at HIST1H2BE histone cluster 1, H2be 8344 −1.05374 0.035992 0.658786 203708_at PDE4B phosphodiesterase 4B, cAMP-specific 5142 −1.26501 0.039076 0.662929 212488_at COL5A1 collagen, type V, alpha 1 1289 −1.01422 0.041826 0.666611 203140_at BCL6 B-cell CLL/lymphoma 6 604 −1.00963 0.04395 0.666724 208546_x_at HIST1H2BH histone cluster 1, H2bh 8345 −1.02623 0.048771 0.677506 214455_at HIST1H2BC histone cluster 1, H2bc 8347 −1.16847 0.051456 0.680853 218999_at TMEM140 transmembrane protein 140 55281 −1.01862 0.053069 0.682752 208018_s_at HCK hemopoietic cell kinase 3055 −1.13981 0.05449 0.684183 204897_at PTGER4 prostaglandin E receptor 4 (subtype 5734 −1.13843 0.058834 0.692792 EP4) 201565_s_at ID2 inhibitor of DNA binding 2, dominant 3398 −1.33513 0.06594 0.694022 negative helix-loop-helix protein 212587_s_at PTPRC protein tyrosine phosphatase, receptor 5788 −1.10126 0.080672 0.719636 type, C 200897_s_at PALLD palladin, cytoskeletal associated protein 23022 −1.24085 0.085951 0.722194 208891_at DUSP6 dual specificity phosphatase 6 1848 −1.07107 0.098612 0.730122 202391_at BASP1 brain abundant, membrane attached 10409 −1.1892 0.099272 0.730445 signal protein 1 201743_at CD14 CD14 molecule 929 −1.11579 0.106127 0.731069 221841_s_at KLF4 Kruppel-like factor 4 (gut) 9314 −1.20574 0.106845 0.731355 206110_at HIST1H3H histone cluster 1, H3h 8357 −1.19698 0.116318 0.738259 213975_s_at LYZ lysozyme 4069 −1.22513 0.117821 0.738667 218723_s_at RGCC regulator of cell cycle 28984 −1.01755 0.173123 0.764957 202917_s_at S100A8 S100 calcium binding protein A8 6279 −1.01114 0.365329 0.843162 209774_x_at CXCL2 chemokine (C—X—C motif) ligand 2 2920 1.127083 0.184971 0.770504 206488_s_at CD36 CD36 molecule (thrombospondin 948 1.062242 0.179158 0.767834 receptor) 206049_at SELP selectin P (granule membrane protein 6403 1.027039 0.142209 0.749649 140 kDa, antigen CD62) 202581_at HSPA1A heat shock 70 kDa protein 1A 3303 1.07338 0.141805 0.749649 212671_s_at HLA-DQA1 major histocompatibility complex, class 3117 1.256994 0.134567 0.747232 II, DQ alpha 1 207808_s_at PROS1 protein S (alpha) 5627 1.076302 0.125868 0.743062 204419_x_at HBG1 hemoglobin, gamma A 3047 1.666375 0.091429 0.723603 204848_x_at HBG1 hemoglobin, gamma A 3047 1.565419 0.086123 0.722194 209839_at DNM3 dynamin 3 26052 1.130837 0.075473 0.711904 217388_s_at KYNU kynureninase 8942 1.468314 0.069766 0.703289 214710_s_at CCNB1 cyclin B1 891 1.019442 0.057837 0.692792 202729_s_at LTBP1 latent transforming growth factor beta 4052 1.205454 0.056194 0.689409 binding protein 1 205950_s_at CA1 carbonic anhydrase I 759 1.154113 0.05527 0.686498 201014_s_at PAICS phosphoribosylaminoimidazole 10606 1.001269 0.054655 0.684183 carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase 215813_s_at PTGS1 prostaglandin-endoperoxide synthase 1 5742 1.093699 0.054246 0.684183 (prostaglandin G/H synthase and cyclooxygenase) 216063_at HBBP1 hemoglobin, beta pseudogene 1 3044 1.237304 0.051626 0.680853 209290_s_at NFIB nuclear factor I/B 4781 1.089323 0.047583 0.675495 212224_at ALDH1A1 aldehyde dehydrogenase 1 family, 216 1.365131 0.047481 0.675495 member A1 207165_at HMMR hyaluronan-mediated motility receptor 3161 1.035451 0.04372 0.666724 (RHAMM) 207668_x_at PDIA6 protein disulfide isomerase family A, 10130 1.01888 0.042673 0.666611 member 6 208639_x_at PDIA6 protein disulfide isomerase family A, 10130 1.087019 0.04232 0.666611 member 6 201202_at PCNA proliferating cell nuclear antigen 5111 1.025175 0.040518 0.664974 202705_at CCNB2 cyclin B2 9133 1.000457 0.037459 0.658786 202870_s_at CDC20 cell division cycle 20 991 1.339489 0.036577 0.658786 217232_x_at HBB hemoglobin, beta 3043 1.819046 0.034587 0.658786 218009_s_at PRC1 protein regulator of cytokinesis 1 9055 1.316131 0.032297 0.65293 213515_x_at HBG1 hemoglobin, gamma A 3047 2.417287 0.029879 0.651733 218350_s_at GMNN geminin, DNA replication inhibitor 51053 1.197599 0.02966 0.651733 209728_at HLA-DRB4 major histocompatibility complex, class 3126 2.147596 0.028176 0.645955 II, DR beta 4 204023_at RFC4 replication factor C (activator 1) 4, 5984 1.139793 0.027395 0.640611 37 kDa 203755_at BUB1B BUB1 mitotic checkpoint 701 1.078262 0.026537 0.639024 serine/threonine kinase B 202760_s_at AKAP2 A kinase (PRKA) anchor protein 2 11217 1.132676 0.023696 0.635738 201477_s_at RRM1 ribonucleotide reductase M1 6240 1.170464 0.02268 0.635738 218039_at NUSAP1 nucleolar and spindle associated protein 1 51203 1.296022 0.022485 0.634539 209773_s_at RRM2 ribonucleotide reductase M2 6241 1.767338 0.021614 0.631601 206632_s_at APOBEC3B apolipoprotein B mRNA editing 9582 1.217919 0.021271 0.631601 enzyme, catalytic polypeptide-like 3B 201563_at SORD sorbitol dehydrogenase 6652 1.003384 0.021071 0.631601 211696_x_at HBB hemoglobin, beta 3043 1.960803 0.020716 0.631601 201490_s_at PPIF peptidylprolyl isomerase F 10105 1.068584 0.02005 0.62633 209969_s_at STAT1 signal transducer and activator of 6772 1.033433 0.018323 0.612297 transcription 1, 91 kDa 202112_at VWF von Willebrand factor 7450 1.065252 0.017067 0.610194 211005_at LAT linker for activation of T cells 27040 1.441264 0.016468 0.605865 206102_at GINS1 GINS complex subunit 1 (Psf1 9837 1.19856 0.014854 0.595174 homolog) 206698_at XK X-linked Kx blood group (McLeod 7504 1.473769 0.014747 0.595174 syndrome) 201761_at MTHFD2 methylenetetrahydrofolate 10797 1.176486 0.01448 0.595174 dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase 202589_at TYMS thymidylate synthetase 7298 1.284352 0.014339 0.594132 203362_s_at MAD2L1 MAD2 mitotic arrest deficient-like 1 4085 1.12377 0.014136 0.591776 (yeast) 204146_at RAD51AP1 RAD51 associated protein 1 10635 1.138009 0.013242 0.587079 202814_s_at HEXIM1 hexamethylene bis-acetamide inducible 1 10614 1.018846 0.011855 0.587079 211953_s_at IPO5 importin 5 3843 1.1663 0.010926 0.587079 212589_at RRAS2 related RAS viral (r-ras) oncogene 22800 1.248922 0.010896 0.587079 homolog 2 201897_s_at CKS1B CDC28 protein kinase regulatory 1163 1.237742 0.010699 0.587079 subunit 1B 201829_at NET1 neuroepithelial cell transforming 1 10276 1.249173 0.010403 0.58573 212459_x_at SUCLG2 succinate-CoA ligase, GDP-forming, 8801 1.16554 0.009868 0.58573 beta subunit 201930_at MCM6 minichromosome maintenance complex 4175 1.046236 0.009628 0.582356 component 6 209116_x_at HBB hemoglobin, beta 3043 2.529691 0.008816 0.568066 218585_s_at DTL denticleless E3 ubiquitin protein ligase 51514 1.376897 0.008767 0.568066 homolog (Drosophila) 206937_at SPTA1 spectrin, alpha, erythrocytic 1 6708 1.114075 0.008321 0.566014 (elliptocytosis 2) 218883_s_at MLF1IP MLF1 interacting protein 79682 1.136186 0.008177 0.566014 215772_x_at SUCLG2 succinate-CoA ligase, GDP-forming, 8801 1.175819 0.008054 0.566014 beta subunit 213088_s_at DNAJC9 DnaJ (Hsp40) homolog, subfamily C, 23234 1.00079 0.007957 0.565327 member 9 206145_at RHAG Rh-associated glycoprotein 6005 1.393541 0.006392 0.547427 204695_at CDC25A cell division cycle 25A 993 1.084134 0.006299 0.547427 204240_s_at SMC2 structural maintenance of chromosomes 2 10592 1.294656 0.005936 0.540991 202107_s_at MCM2 minichromosome maintenance complex 4171 1.222252 0.005761 0.536001 component 2 222204_s_at RRN3 RRN3 RNA polymerase I transcription 54700 1.042118 0.005729 0.536001 factor homolog (S. cerevisiae) 203560_at GGH gamma-glutamyl hydrolase (conjugase, 8836 1.340214 0.00547 0.526569 folylpolygammaglutamyl hydrolase) 202613_at CTPS1 CTP synthase 1 1503 1.14984 0.005331 0.526569 208955_at DUT deoxyuridine triphosphatase 1854 1.03421 0.005157 0.523702 212282_at TMEM97 transmembrane protein 97 27346 1.011374 0.004822 0.516178 219412_at RAB38 RAB38, member RAS oncogene family 23682 1.168702 0.004753 0.516178 202503_s_at KIAA0101 KIAA0101 9768 1.309228 0.00471 0.516178 204767_s_at FEN1 flap structure-specific endonuclease 1 2237 1.381621 0.004647 0.516178 205394_at CHEK1 checkpoint kinase 1 1111 1.045411 0.004442 0.516178 201489_at PPIF peptidylprolyl isomerase F 10105 1.118185 0.004062 0.507454 201890_at RRM2 ribonucleotide reductase M2 6241 2.141038 0.00366 0.47601 219306_at KIF15 kinesin family member 15 56992 1.266139 0.003389 0.461859 211144_x_at TARP TCR gamma alternate reading frame 445347 1.260002 0.003285 0.456931 protein 206834_at HBD hemoglobin, delta 3045 2.172202 0.003266 0.456931 203476_at TPBG trophoblast glycoprotein 7162 1.132385 0.002991 0.450281 212281_s_at TMEM97 transmembrane protein 97 27346 1.2802 0.002875 0.450281 206067_s_at WT1 Wilms tumor 1 7490 1.247746 0.002812 0.450281 208694_at PRKDC protein kinase, DNA-activated, catalytic 5591 1.067872 0.002544 0.438543 polypeptide 206118_at STAT4 signal transducer and activator of 6775 1.012186 0.002506 0.438543 transcription 4 216920_s_at TARP TCR gamma alternate reading frame 445347 1.474096 0.002252 0.428068 protein 202949_s_at FHL2 four and a half LIM domains 2 2274 1.107316 0.002224 0.428068 222201_s_at CASP8AP2 caspase 8 associated protein 2 9994 1.054149 0.001764 0.399532 204026_s_at ZWINT ZW10 interactor, kinetochore protein 11130 1.720113 0.001341 0.397293 209894_at LEPR leptin receptor 3953 2.015714 0.001141 0.380525 213092_x_at DNAJC9 DnaJ (Hsp40) homolog, subfamily C, 23234 1.090583 0.000823 0.310206 member 9 219454_at EGFL6 EGF-like-domain, multiple 6 25975 1.45589 0.000616 0.258418 213262_at SACS spastic ataxia of Charlevoix-Saguenay 26278 1.042232 0.00059 0.252396 (sacsin) 204256_at ELOVL6 ELOVL fatty acid elongase 6 79071 1.448618 0.000559 0.252191 215806_x_at TARP TCR gamma alternate reading frame 445347 1.534041 0.000427 0.227751 protein 209813_x_at TARP TCR gamma alternate reading frame 445347 1.665423 0.000291 0.215629 protein 201830_s_at NET1 neuroepithelial cell transforming 1 10276 1.530152 0.000251 0.213741 219615_s_at KCNK5 potassium channel, subfamily K, 8645 1.04543 0.000225 0.21202 member 5 219602_s_at PIEZO2 piezo-type mechanosensitive ion 63895 1.504577 7.50E−05 0.117928 channel component 2 219000_s_at DSCC1 defective in sister chromatid cohesion 1 79075 1.081581 4.67E−05 0.079813 homolog (S. cerevisiae) 205848_at GAS2 growth arrest-specific 2 2620 2.492596 1.11E−05 0.02744

TABLE 10 Gene Expression in the Aggressive Group of the Core 102 Genes Symbol (Na32 GeneID consesus Gene Title (Na32 consensus (NCBI Adjusted Probeset ID Mar13) Mar13) Mar) Log2 (FC) P-Value p-Value 209763_at CHRDL1 chordin-like 1 91851 −1.1760592 5.21E−09 6.67E−05 210487_at DNTT deoxynucleotidyltransferase, 1791 −1.91383418 6.00E−09 6.67E−05 terminal 205933_at SETBP1 SET binding protein 1 26040 −1.17729694 1.51E−08 0.0001121 201324_at EMP1 epithelial membrane protein 1 2012 −1.73634604 6.04E−06 0.0268018 209183_s_at C10orf10 chromosome 10 open reading 11067 −1.07496461 0.000131314 0.1390556 frame 10 209374_s_at IGHM immunoglobulin heavy constant 3507 −1.78677828 0.000238354 0.2120204 mu 204430_s_at SLC2A5 solute carrier family 2 6518 −1.13053427 0.000259511 0.2137408 (facilitated glucose/fructose transporter), member 5 209069_s_at H3F3B H3 histone, family 3B (H3.3B) 3021 −1.18660722 0.0003182 0.221129 219777_at GIMAP6 GTPase, IMAP family member 6 474344 −0.96412142 0.000351795 0.2277507 204304_s_at PROM1 prominin 1 8842 −1.82998841 0.000419599 0.2277507 205984_at CRHBP corticotropin releasing hormone 1393 −1.68558627 0.000481558 0.2391606 binding protein 211998_at H3F3B H3 histone, family 3B (H3.3B) 3021 −1.37160868 0.00110064 0.3765544 220990_s_at MIR21 microRNA 21 406991 −1.1666179 0.002023122 0.4125343 201369_s_at ZFP36L2 ZFP36 ring finger protein-like 2 678 −1.42931862 0.002728865 0.4502813 204872_at TLE4 transducin-like enhancer of split 7091 −1.08661045 0.004743456 0.5161776 4 (E(sp1) homolog, Drosophila) 211597_s_at HOPX HOP homeobox 84525 −1.35699251 0.004786898 0.5161776 220377_at KIAA0125 KIAA0125 9834 −1.15784914 0.004956965 0.5161776 219304_s_at PDGFD platelet derived growth factor D 80310 −0.94059913 0.005103212 0.5229734 208960_s_at KLF6 Kruppel-like factor 6 1316 −0.94664654 0.010221625 0.5857297 203787_at SSBP2 single-stranded DNA binding 23635 −0.79229496 0.013428932 0.5870789 protein 2 204755_x_at HLF hepatic leukemia factor 3131 −0.61251884 0.013936253 0.5899467 209576_at GNAI1 guanine nucleotide binding 2770 −0.63080373 0.015529376 0.6015332 protein (G protein), alpha inhibiting activity polypeptide 1 204753_s_at HLF hepatic leukemia factor 3131 −0.70807109 0.021022562 0.6316009 221760_at MAN1A1 mannosidase, alpha, class 1A, 4121 −1.18371513 0.022329984 0.6327526 member 1 206478_at KIAA0125 KIAA0125 9834 −0.99597623 0.02539777 0.6372958 221556_at CDC14B cell division cycle 14B 8555 −1.26288843 0.028047825 0.6449399 214805_at EIF4A1 eukaryotic translation initiation 1973 −0.67982725 0.028070099 0.6449399 factor 4A1 220416_at ATP8B4 ATPase, class I, type 8B, 79895 −0.73256572 0.031829237 0.6529304 member 4 208835_s_at LUC7L3 LUC7-like 3 (S. cerevisiae) 51747 −0.90441159 0.042521869 0.666611 204030_s_at IQCJ-SCHIP1 IQCJ-SCHIP1 readthrough 100505385 −0.57342 0.042715691 0.666611 204897_at PTGER4 prostaglandin E receptor 4 5734 −1.13842542 0.058834073 0.6927923 (subtype EP4) 208949_s_at LGALS3 lectin, galactoside-binding, 3958 −0.78834036 0.075957894 0.7119044 soluble, 3 208961_s_at KLF6 Kruppel-like factor 6 1316 −0.79400193 0.078101123 0.7129149 209112_at CDKN1B cyclin-dependent kinase 1027 −0.57998283 0.119332543 0.7386668 inhibitor 1B (p27, Kip1) 204563_at SELL selectin L 6402 −0.97868544 0.120606528 0.7393127 214651_s_at HOXA9 homeobox A9 3205 −0.56640825 0.211940371 0.7838234 208892_s_at DUSP6 dual specificity phosphatase 6 1848 −0.85096752 0.235607663 0.7928467 213524_s_at G0S2 G0/G1 switch 2 50486 −0.82501945 0.239215682 0.7948695 203535_at S100A9 S100 calcium binding protein 6280 −0.80627992 0.254346668 0.8015736 A9 213668_s_at SOX4 SRY (sex determining region 6659 −0.82323589 0.260556623 0.802741 Y)-box 4 222044_at PCIF1 PDX1 C-terminal inhibiting 63935 −0.49806168 0.282560332 0.8109941 factor 1 213593_s_at TRA2A transformer 2 alpha homolog 29896 −0.60971572 0.344365936 0.8383152 (Drosophila) 214041_x_at RPL37A ribosomal protein L37a 6168 −0.39653673 0.407444152 0.8568069 205442_at MFAP3L microfibrillar-associated protein 9848 −0.51285589 0.449796577 0.8725199 3-like 214974_x_at CXCL5 chemokine (C—X—C motif) ligand 5 6374 −0.41826978 0.551543186 0.9009074 213979_s_at — — −0.35065846 0.599848748 0.9149341 214911_s_at BRD2 bromodomain containing 2 6046 −0.27608523 0.611740131 0.9174215 211074_at FOLR1 folate receptor 1 (adult) 2348 −0.45112625 0.632000886 0.9246948 208180_s_at HIST1H4H histone cluster 1, H4h 8365 −0.2778544 0.639528185 0.9257406 207815_at PF4V1 platelet factor 4 variant 1 5197 −0.30911148 0.651979155 0.9286903 205547_s_at TAGLN transgelin 6876 −0.28088743 0.708017145 0.9439304 205237_at FCN1 ficolin (collagen/fibrinogen 2219 −0.32136788 0.711156716 0.944669 domain containing) 1 219922_s_at LTBP3 latent transforming growth factor 4054 −0.18060244 0.723881126 0.9484945 beta binding protein 3 204141_at TUBB2A tubulin, beta 2A class IIa 7280 −0.29534658 0.735081772 0.9498889 212952_at LOC100507328 hypothetical LOC100507328 100507328 −0.22415499 0.743954062 0.9528039 209803_s_at PHLDA2 pleckstrin homology-like 7262 −0.19751659 0.762353226 0.9568355 domain, family A, member 2 204834_at FGL2 fibrinogen-like 2 10875 −0.20803456 0.771018008 0.9582727 213350_at RPS11 ribosomal protein S11 6205 −0.21555457 0.772923808 0.9589509 211964_at COL4A2 collagen, type IV, alpha 2 1284 −0.15879898 0.78084214 0.9613311 205114_s_at CCL3L3 chemokine (C-C motif) ligand 3- 414062 −0.20519345 0.793565216 0.9626063 like 3 202310_s_at COL1A1 collagen, type I, alpha 1 1277 −0.22272495 0.796823974 0.9633788 217683_at HBE1 hemoglobin, epsilon 1 3046 −0.12978731 0.806948287 0.964919 201842_s_at EFEMP1 EGF containing fibulin-like 2202 −0.17500966 0.813572867 0.9663992 extracellular matrix protein 1 201631_s_at IER3 immediate early response 3 8870 −0.12662907 0.836432308 0.9684535 201798_s_at MYOF myoferlin 26509 −0.12987194 0.839316831 0.9692311 1405_i_at CCL5 chemokine (C-C motif) ligand 5 6352 −0.16353025 0.840439597 0.9695199 201058_s_at MYL9 myosin, light chain 9, regulatory 10398 −0.11665284 0.854796069 0.9731863 215076_s_at COL3A1 collagen, type III, alpha 1 1281 −0.11954993 0.877410108 0.9785103 202403_s_at COL1A2 collagen, type I, alpha 2 1278 −0.11102553 0.891268391 0.9806744 210809_s_at POSTN periostin, osteoblast specific 10631 −0.1111146 0.912911705 0.9851423 factor 212531_at LCN2 lipocalin 2 3934 −0.02914052 0.962852347 0.9923439 210873_x_at APOBEC3A apolipoprotein B mRNA editing 200315 −0.02534114 0.967184016 0.9940037 enzyme, catalytic polypeptide- like 3A 211980_at COL4A1 collagen, type IV, alpha 1 1282 −0.01874739 0.977820792 0.9959916 201438_at COL6A3 collagen, type VI, alpha 3 1293 0.009703779 0.9863171 0.9970689 74694_s_at RABEP2 rabaptin, RAB GTPase binding 79874 0.011843173 0.981583585 0.9961445 effector protein 2 211719_x_at FN1 fibronectin 1 2335 0.037210894 0.973177363 0.9950096 202404_s_at COL1A2 collagen, type I, alpha 2 1278 0.034227062 0.972988883 0.9950096 204655_at CCL5 chemokine (C-C motif) ligand 5 6352 0.038628831 0.965309914 0.9935003 216442_x_at FN1 fibronectin 1 2335 0.054191701 0.95355946 0.9912349 210495_x_at FN1 fibronectin 1 2335 0.058226728 0.951550365 0.9910374 212464_s_at FN1 fibronectin 1 2335 0.081392657 0.933688332 0.988994 211161_s_at COL3A1 collagen, type III, alpha 1 1281 0.056146834 0.930500411 0.9881951 212667_at SPARC secreted protein, acidic, 6678 0.058151732 0.926810399 0.9875364 cysteine-rich (osteonectin) 202627_s_at SERPINE1 serpin peptidase inhibitor, clade 5054 0.130825837 0.842575178 0.9702264 E (nexin, plasminogen activator inhibitor type 1), member 1 213757_at EIF5A eukaryotic translation initiation 1984 0.138314467 0.836269539 0.9684535 factor 5A 202600_s_at NRIP1 nuclear receptor interacting 8204 0.146667606 0.81125437 0.9660204 protein 1 202237_at NNMT nicotinamide N- 4837 0.357137196 0.643404225 0.9262055 methyltransferase 201666_at TIMP1 TIMP metallopeptidase inhibitor 1 7076 0.178832267 0.632222051 0.9248966 204018_x_at HBA1 hemoglobin, alpha 1 3039 0.503353692 0.544752592 0.8986814 200999_s_at CKAP4 cytoskeleton-associated protein 4 10970 0.335798499 0.541539556 0.8965721 204622_x_at NR4A2 nuclear receptor subfamily 4, 4929 0.334447219 0.497538974 0.8848345 group A, member 2 203394_s_at HES1 hairy and enhancer of split 1, 3280 0.443814733 0.487186309 0.8828267 (Drosophila) 206157_at PTX3 pentraxin 3, long 5806 0.494269798 0.426649316 0.8638802 205382_s_at CFD complement factor D (adipsin) 1675 0.493713983 0.395763648 0.8528093 217414_x_at HBA1 hemoglobin, alpha 1 3039 0.792680859 0.377115905 0.8469171 211745_x_at HBA1 hemoglobin, alpha 1 3039 0.872403284 0.371311295 0.8441546 214414_x_at HBA1 hemoglobin, alpha 1 3039 0.997898457 0.369791698 0.8441546 211699_x_at HBA1 hemoglobin, alpha 1 3039 0.740693292 0.368184583 0.844099 209458_x_at HBA1 hemoglobin, alpha 1 3039 0.850433299 0.356237193 0.8404624 212077_at CALD1 caldesmon 1 800 0.588320285 0.348578502 0.8401911 216248_s_at NR4A2 nuclear receptor subfamily 4, 4929 0.570789503 0.342393968 0.8375489 group A, member 2 219403_s_at HPSE heparanase 10855 0.691038194 0.269546864 0.8062958 201110_s_at THBS1 thrombospondin 1 7057 0.670401219 0.251133297 0.8008466 203395_s_at HES1 hairy and enhancer of split 1, 3280 0.85070808 0.193692 0.7743035 (Drosophila) 200629_at WARS tryptophanyl-tRNA synthetase 7453 0.666045516 0.186006457 0.7721508 201669_s_at MARCKS myristoylated alanine-rich 4082 0.759568605 0.132720593 0.7472316 protein kinase C substrate 201195_s_at SLC7A5 solute carrier family 7 (amino 8140 0.824741527 0.116329142 0.7382591 acid transporter light chain, L system), member 5 204419_x_at HBG1 hemoglobin, gamma A 3047 1.666375122 0.09142905 0.723603 204848_x_at HBG1 hemoglobin, gamma A 3047 1.565419124 0.086123226 0.7221941 219410_at TMEM45A transmembrane protein 45A 55076 0.991276475 0.082130669 0.7221941 217388_s_at KYNU kynureninase 8942 1.468313974 0.069766007 0.7032894 209290_s_at NFIB nuclear factor I/B 4781 1.089323355 0.04758335 0.6754948 202870_s_at CDC20 cell division cycle 20 991 1.339488946 0.036576735 0.658786 217232_x_at HBB hemoglobin, beta 3043 1.819045943 0.03458682 0.658786 213515_x_at HBG1 hemoglobin, gamma A 3047 2.417286959 0.029878597 0.651733 209773_s_at RRM2 ribonucleotide reductase M2 6241 1.767337745 0.021613828 0.6316009 211696_x_at HBB hemoglobin, beta 3043 1.960802898 0.020715624 0.6316009 206698_at XK X-linked Kx blood group 7504 1.473769082 0.01474655 0.5951742 (McLeod syndrome) 212589_at RRAS2 related RAS viral (r-ras) 22800 1.248921748 0.010895573 0.5870789 oncogene homolog 2 209116_x_at HBB hemoglobin, beta 3043 2.529691269 0.008815809 0.5680662 215772_x_at SUCLG2 succinate-CoA ligase, GDP- 8801 1.175819449 0.008054348 0.5660139 forming, beta subunit 201890_at RRM2 ribonucleotide reductase M2 6241 2.141037934 0.003660296 0.4760098 209894_at LEPR leptin receptor 3953 2.015713837 0.00114085 0.3805249 219602_s_at PIEZO2 piezo-type mechanosensitive ion 63895 1.504577032 7.50E−05 0.1179278 channel component 2 205848_at GAS2 growth arrest-specific 2 2620 2.492595762 1.11E−05 0.0274403

TABLE 11 Gene Expression in the Indolent Group of the Core 102 Genes Symbol (Na32 GeneID consensus Gene Title (Na32 consensus (consensus1 Adjusted Probeset ID Mar13) Mar13) Mar-13) Log2 (FC) P-Value p-Value 208949_s_at LGALS3 lectin, galactoside-binding, 3958 −2.46115508 4.71E−07 0.0008705 soluble, 3 201666_at TIMP1 TIMP metallopeptidase inhibitor 1 7076 −1.63941887 2.35E−05 0.0042807 201058_s_at MYL9 myosin, light chain 9, regulatory 10398 −2.74636917 3.07E−05 0.0046717 207815_at PF4V1 platelet factor 4 variant 1 5197 −2.82238801 5.35E−05 0.0058277 1405_i_at CCL5 chemokine (C-C motif) ligand 5 6352 −3.32636522 5.85E−05 0.0060359 213524_s_at G0S2 G0/G1switch 2 50486 −2.65614662 0.0001262 0.007998 201631_s_at IER3 immediate early response 3 8870 −2.29780898 0.000169 0.009257 204655_at CCL5 chemokine (C-C motif) ligand 5 6352 −3.23424391 0.0002336 0.0105336 203535_at S100A9 S100 calcium binding protein A9 6280 −2.4351969 0.0003703 0.0133722 212077_at CALD1 caldesmon 1 800 −2.04255108 0.0006877 0.0178246 210873_x_at APOBEC3A apolipoprotein B mRNA editing 200315 −1.76920321 0.0023357 0.032102 enzyme, catalytic polypeptide- like 3A 212531_at LCN2 lipocalin 2 3934 −1.74944593 0.0029164 0.0363335 205114_s_at CCL3L3 chemokine (C-C motif) ligand 3- 414062 −2.11268057 0.0038941 0.0419976 like 3 208180_s_at HIST1H4H histone cluster 1, H4h 8365 −1.58614736 0.0040832 0.0431848 205237_at FCN1 ficolin (collagen/fibrinogen 2219 −2.31794481 0.0041427 0.0434495 domain containing) 1 214414_x_at HBA1 hemoglobin, alpha 1 3039 −2.92561932 0.0044286 0.0449487 209803_s_at PHLDA2 pleckstrin homology-like 7262 −1.71861099 0.0046599 0.0462831 domain, family A, member 2 201438_at COL6A3 collagen, type VI, alpha 3 1293 −1.45596175 0.0055357 0.0504893 205547_s_at TAGLN transgelin 6876 −1.89686803 0.0062053 0.0538116 211074_at FOLR1 folate receptor 1 (adult) 2348 −2.33500441 0.0071061 0.0579213 221556_at CDC14B cell division cycle 14B 8555 −1.35462909 0.0072261 0.0582223 211745_x_at HBA1 hemoglobin, alpha 1 3039 −2.39194906 0.0073721 0.0586827 204141_at TUBB2A tubulin, beta 2A class IIa 7280 −2.13929618 0.0077476 0.0602366 204018_x_at HBA1 hemoglobin, alpha 1 3039 −1.9801303 0.0092138 0.0661068 201798_s_at MYOF myoferlin 26509 −1.51465891 0.009894 0.0682173 209458_x_at HBA1 hemoglobin, alpha 1 3039 −2.13257405 0.0108016 0.071832 217414_x_at HBA1 hemoglobin, alpha 1 3039 −2.0496731 0.0117787 0.0752125 211964_at COL4A2 collagen, type IV, alpha 2 1284 −1.30406638 0.0122956 0.0767626 205442_at MFAP3L microfibrillar-associated protein 9848 −1.52050559 0.0134371 0.0808545 3-like 214974_x_at CXCL5 chemokine (C—X—C motif) ligand 5 6374 −1.55942048 0.0144079 0.083963 202310_s_at COL1A1 collagen, type I, alpha 1 1277 −1.87618778 0.0168309 0.0918907 219403_s_at HPSE heparanase 10855 −1.31934206 0.0184966 0.0968056 212667_at SPARC secreted protein, acidic, cysteine- 6678 −1.34731184 0.0188123 0.0976538 rich (osteonectin) 200999_s_at CKAP4 cytoskeleton-associated protein 4 10970 −1.14939507 0.0204052 0.1017426 204834_at FGL2 fibrinogen-like 2 10875 −1.46819648 0.0227746 0.1072555 216442_x_at FN1 fibronectin 1 2335 −1.90725545 0.023141 0.1081658 201842_s_at EFEMP1 EGF containing fibulin-like 2202 −1.50062086 0.0247947 0.1121383 extracellular matrix protein 1 212464_s_at FN1 fibronectin 1 2335 −1.96352838 0.0258307 0.1143867 211719_x_at FN1 fibronectin 1 2335 −2.20581999 0.0267964 0.1164775 210495_x_at FN1 fibronectin 1 2335 −1.90768224 0.026965 0.1168453 216248_s_at NR4A2 nuclear receptor subfamily 4, 4929 −1.17498747 0.0282382 0.1197257 group A, member 2 211699_x_at HBA1 hemoglobin, alpha 1 3039 −1.60001534 0.0291616 0.1216234 217683_at HBE1 hemoglobin, epsilon 1 3046 −1.01631722 0.0327501 0.1295902 202627_s_at SERPINE1 serpin peptidase inhibitor, clade 5054 −1.241552 0.0352569 0.1349566 E (nexin, plasminogen activator inhibitor type 1), member 1 203394_s_at HES1 hairy and enhancer of split 1, 3280 −1.1913737 0.0362517 0.1371457 (Drosophila) 211980_at COL4A1 collagen, type IV, alpha 1 1282 −1.25680354 0.0372348 0.139094 204622_x_at NR4A2 nuclear receptor subfamily 4, 4929 −0.91072954 0.037958 0.1405444 group A, member 2 215076_s_at COL3A1 collagen, type III, alpha 1 1281 −1.43307205 0.0385845 0.1417739 202403_s_at COL1A2 collagen, type I, alpha 2 1278 −1.44054881 0.0465026 0.1564484 202404_s_at COL1A2 collagen, type I, alpha 2 1278 −1.71166248 0.0565387 0.1733135 210809_s_at POSTN periostin, osteoblast specific 10631 −1.70047318 0.0592192 0.1779858 factor 200629_at WARS tryptophanyl-tRNA synthetase 7453 −0.81407303 0.0632647 0.1842488 205382_s_at CFD complement factor D (adipsin) 1675 −0.93430533 0.0674121 0.1911642 211161_s_at COL3A1 collagen, type III, alpha 1 1281 −0.97790719 0.0849171 0.216434 202237_at NNMT nicotinamide N- 4837 −1.16905976 0.0849883 0.216541 methyltransferase 206157_at PTX3 pentraxin 3, long 5806 −0.8886965 0.1017166 0.2401657 222044_at PCIF1 PDX1 C-terminal inhibiting 63935 −0.59010446 0.1405898 0.2902372 factor 1 203395_s_at HES1 hairy and enhancer of split 1, 3280 −0.82856755 0.1406431 0.2902934 (Drosophila) 214041_x_at RPL37A ribosomal protein L37a 6168 −0.49636026 0.2288142 0.3892891 213668_s_at SOX4 SRY (sex determining region Y)- 6659 −0.74126503 0.2366512 0.397241 box 4 214911_s_at BRD2 bromodomain containing 2 6046 −0.55589849 0.237402 0.3980366 213515_x_at HBG1 hemoglobin, gamma A 3047 −1.06377 0.2466641 0.407885 204419_x_at HBG1 hemoglobin, gamma A 3047 −0.908371 0.2734668 0.4340414 208892_s_at DUSP6 dual specificity phosphatase 6 1848 −0.62624686 0.3054404 0.4659019 201669_s_at MARCKS myristoylated alanine-rich 4082 −0.4343098 0.308411 0.4689854 protein kinase C substrate 201324_at EMP1 epithelial membrane protein 1 2012 −0.26518451 0.3157697 0.476429 204848_x_at HBG1 hemoglobin, gamma A 3047 −0.73774161 0.3338994 0.4939304 213350_at RPS11 ribosomal protein S11 6205 −0.59851213 0.3525386 0.5113994 213593_s_at TRA2A transformer 2 alpha homolog 29896 −0.51180921 0.3529863 0.5117818 (Drosophila) 209374_s_at IGHM immunoglobulin heavy constant 3507 −0.31785029 0.3800608 0.5367239 mu 213979_s_at — — — −0.40184672 0.4828663 0.6262323 201110_s_at THBS1 thrombospondin 1 7057 −0.32862948 0.50663 0.645676 212952_at LOC100507328 hypothetical LOC100507328 100507328 −0.3705879 0.5288342 0.6639313 213757_at EIF5A eukaryotic translation initiation 1984 −0.30685777 0.5926473 0.7155269 factor 5A 201195_s_at SLC7A5 solute carrier family 7 (amino 8140 −0.21795555 0.6192996 0.7368622 acid transporter light chain, L system), member 5 217232_x_at HBB hemoglobin, beta 3043 −0.28037802 0.690155 0.7905057 206698_at XK X-linked Kx blood group 7504 −0.15354275 0.7519213 0.8333529 (McLeod syndrome) 209116_x_at HBB hemoglobin, beta 3043 −0.22011194 0.7745612 0.8490507 208960_s_at KLF6 Kruppel-like factor 6 1316 −0.0669692 0.8198308 0.8804886 211696_x_at HBB hemoglobin, beta 3043 −0.11853666 0.8626478 0.9090874 212589_at RRAS2 related RAS viral (r-ras) 22800 −0.03039679 0.9381282 0.9597619 oncogene homolog 2 74694_s_at RABEP2 rabaptin, RAB GTPase binding 79874 −0.02974959 0.9459227 0.9655037 effector protein 2 205933_at SETBP1 SET binding protein 1 26040 −0.00557713 0.9639004 0.976948 219410_at TMEM45A transmembrane protein 45A 55076 −0.01300971 0.9780245 0.9864563 209183_s_at C10orf10 chromosome 10 open reading 11067 0.053999237 0.7924264 0.8612892 frame 10 217388_s_at KYNU kynureninase 8942 0.220147884 0.7422951 0.8265151 204872_at TLE4 transducin-like enhancer of split 7091 0.119923227 0.6919854 0.7913794 4 (E(sp1) homolog, Drosophila) 209290_s_at NFIB nuclear factor I/B 4781 0.179441546 0.6912758 0.7909339 209069_s_at H3F3B H3 histone, family 3B (H3.3B) 3021 0.099846114 0.6841093 0.7862131 209763_at CHRDL1 chordin-like 1 91851 0.050254159 0.6660676 0.7731502 208961_s_at KLF6 Kruppel-like factor 6 1316 0.203610948 0.5862653 0.7103285 219922_s_at LTBP3 latent transforming growth factor 4054 0.265731289 0.5441646 0.676381 beta binding protein 3 210487_at DNTT deoxynucleotidyltransferase, 1791 0.159844182 0.4049727 0.5588841 terminal 202600_s_at NRIP1 nuclear receptor interacting 8204 0.470263901 0.374044 0.5310937 protein 1 211998_at H3F3B H3 histone, family 3B (H3.3B) 3021 0.303014616 0.3488911 0.5083632 219304_s_at PDGFD platelet derived growth factor D 80310 0.277596346 0.298783 0.4593071 204897_at PTGER4 prostaglandin E receptor 4 5734 0.607994686 0.2274529 0.3875045 (subtype EP4) 202870_s_at CDC20 cell division cycle 20 991 0.762009765 0.1538922 0.3060777 220990_s_at MIR21 microRNA 21 406991 0.435464726 0.1444477 0.2949163 220377_at KIAA0125 KIAA0125 9834 0.487203922 0.1414233 0.2913494 215772_x_at SUCLG2 succinate-CoA ligase, GDP- 8801 0.540170913 0.1340248 0.2820253 forming, beta subunit 204563_at SELL selectin L 6402 0.910468161 0.0926084 0.2277875 211597_s_at HOPX HOP homeobox 84525 0.686080974 0.0787633 0.2073318 205984_at CRHBP corticotropin releasing hormone 1393 0.67956433 0.0697279 0.1948001 binding protein 208835_s_at LUC7L3 LUC7-like 3 (S. cerevisiae) 51747 0.690777363 0.0676605 0.1915926 221760_at MAN1A1 mannosidase, alpha, class 1A, 4121 0.824262339 0.0582629 0.1763029 member 1 201369_s_at ZFP36L2 ZFP36 ring finger protein-like 2 678 0.748937338 0.0520224 0.1657888 209773_s_at RRM2 ribonucleotide reductase M2 6241 1.272153164 0.0495607 0.1616025 204304_s_at PROM1 prominin 1 8842 0.925426909 0.0237482 0.1095213 209894_at LEPR leptin receptor 3953 1.184929139 0.0181485 0.0959498 203787_at SSBP2 single-stranded DNA binding 23635 0.75811153 0.0063777 0.0544303 protein 2 201890_at RRM2 ribonucleotide reductase M2 6241 1.743455889 0.0052954 0.0493966 219602_s_at PIEZO2 piezo-type mechanosensitive ion 63895 0.949014365 0.0017907 0.0285001 channel component 2 204755_x_at HLF hepatic leukemia factor 3131 0.692860181 0.0017806 0.0285001 204753_s_at HLF hepatic leukemia factor 3131 0.867266686 0.0016555 0.0275765 209576_at GNAI1 guanine nucleotide binding 2770 0.736228442 0.0015849 0.0269254 protein (G protein), alpha inhibiting activity polypeptide 1 214805_at EIF4A1 eukaryotic translation initiation 1973 0.894052441 0.001431 0.025337 factor 4A1 209112_at CDKN1B cyclin-dependent kinase inhibitor 1027 1.181992974 0.0007491 0.0186168 1B (p27, Kip1) 214651_s_at HOXA9 homeobox A9 3205 1.466348689 0.0006873 0.0178246 219777_at GIMAP6 GTPase, IMAP family member 6 474344 0.787293816 0.000565 0.016422 204430_s_at SLC2A5 solute carrier family 2 (facilitated 6518 0.916940276 0.0004539 0.0149986 glucose/fructose transporter), member 5 206478_at KIAA0125 KIAA0125 9834 1.699585816 7.39E−05 0.0063689 220416_at ATP8B4 ATPase, class I, type 8B, 79895 1.319886477 6.56E−05 0.0061373 member 4 205848_at GAS2 growth arrest-specific 2 2620 1.882945739 5.69E−05 0.0059648 204030_s_at IQCJ-SCHIP1 IQCJ-SCHIP1 readthrough 100505385 1.123786747 5.04E−05 0.0057459

TABLE 12 Regulation of 16 PV Core Genes in Chronic Phase CML CML Chronic Phase CML Blast Phase Up Regulated Genes Up Regulated Genes HBA2 RRAS2 HBB GAS2 HBG1 HES1 COL1A1 EMP1 RRM2 SSBP2 THSB1 LUC7L3 TIMP1 GIMAP6 MARCKS eIF5A XK SETBP1 CDC20 MYOF LEPR CCL5 IER3 KYNU LGALS3 eIF5A HOXA9 Down Regulated Genes Down Regulated Genes SCHIP1 IGHM HLF SELL PROM1 EFEMP1 MAN1A1 HBA1 CRHBP FCN1 KIAA1025 LCN2 DNTT CKAP4 IGHM S100A9 SELL APOBEC3A FGL2 FGL2 NR4A2 IER3 CDC14B G0S2 HES1 LGALS3 NRIP1 SOX4

TABLE 13 10 Gene Screen Probability Score: 30 Test PV Cohort Aggressive (5-6/6) Indolent (0-4/6) P N = 8 N = 22 value Gender (M/F) 1/7 11/11  ns Median Age in Years 62 (46-76) 65 (43-79) ns (range) % JAK2 V617F (range) 94 (52-100) 81 (44-100) ns Leukocyte count 31 14.5 ns Thrombosis 6/8 5/22 0.014 Hemoglobin 10.9 13.1 0.006 Median Disease Duration 15.5 7 0.011 in years (range) Platelet count 308 666 <0.019 Palpable splenomegaly 8/8 9/22 0.009 Spleen size 14 3.5 0.033 Chemotherapy 7/8 7/22 0.012 Median Probability Score 5.0 (5-6) 2.5 (0-4) <0.001 (range) Median Clinical Score 3.0 (2-4) 0 (0-3) <0.001 (range)

TABLE 14 Ten Gene Screening Panel Gene SEQ Target Symbol Gene Name Context Sequence ID No. Exons PCNA proliferating AAAGAGGAGGAAGCTGTTACCATAG 1 5 cell nuclear antigen TSN translin GCCAGTGAACTGTCGAGGCTGTCTG 2 5 CDKN1A cyclin-dependent GCAGACCAGCATGACAGATTTCTAC 3 2 kinase inhibitor 1A (p21, Cip1) MYL9 myosin, light TGGCCTCGCTGGGTTTCATCCATGA 4 2 chain 9, regulatory IFI30 interferon, CTGCCAGTTGTACCAGGGCAAGAAG 5 7 gamma-inducible protein 30 CTSA cathepsin A CAGAAGATGGAGGTGCAGCGCCGGC 6 14  SMC4 structural AAAAGAAGGAAGAATTGTATTTGCA 7 21  maintenance of chromosomes4 CTTN cortactin CTACCAGGCTGCGGGCGATGATGAG 8 16  SON SON DNA CAAACATTTTCTCTTTAGGGTATTG 9 12  binding protein TIA1 TIA1 cytotoxic CCCGTGCAACAGCAGAATCAAATTG 10  10  granule-asociated RNA binding protein ACTB Beta actin 1 (Endogenous control)

TABLE 15 Ten Gene Screening Panel NCBI Gene Accession Nos. Gene Symbol NCBI Gene Accession Nos. PCNA NM_002592, NM_182649 TSN NM_004622 CDKN1A NM_000389, NM_001220777, NM_001220778, NM_078467 MYL9 NM_181526 IFI30 NM_006332 CTSA NM_000308, NM_001127695, NM_001167594 SMC4 NM_001002800, NM_005496 CTTN NM_001184740, NM_005231, NM_138565 SON NM_138927 TIA1 NM_022037, NM_022173 ACTB NM_001101

TABLE 16 Gene Expression Assay Reagents Primer-Probe SEQ Gene Symbol Assay ID Context Symbol ID No. Part Number PCNA Hs00952870_g1 AAAGAGGAGGAAGCTGTTACCATAG 11 4331182 TSN Hs00172824_m1 GCCAGTGAACTGTCGAGGCTGTCTG 12 4331182 CDKN1A Hs00355782_m1 GCAGACCAGCATGACAGATTTCTAC 13 4331182 MYL9 Hs00382913_m1 TGGCCTCGCTGGGTTTCATCCATGA 14 4331182 IFI30 Hs00908857_g1  CTGCCAGTTGTACCAGGGCAAGAAG 15 4351372 CTSA Hs01563956_g1  CAGAAGATGGAGGTGCAGCGCCGGC 16 4351372 SMC4 Hs00909708_g1 AAAAGAAGGAAGAATTGTATTTGCA 17 4351372 CTTN Hs01124227_m1 CTACCAGGCTGCGGGCGATGATGAG 18 4351372 SON Hs01066142_g1 CAAACATTTTCTCTTTAGGGTATTG 19 4351372 TIA1 Hs01046922_m1 CCCGTGCAACAGCAGAATCAAATTG 20 4351372 ACTB N/A N/A  4333762F

TABLE 17 Algorithm for PV Patient Stratification Ten Gene Screening Panel For the following gene level comparisons: If TRUE (and >2 fold difference) score 1 If FALSE (or <2 fold difference) score 0 A score of >4 out of 6 indicates an aggressive form of PV PCNA > IFI30 TSN > CTSA SMC4 > CDKN1A PCNA > CTTN SON > CTTN TIA1 > MYL9

TABLE 18 10 Gene Screening Data from Indolent PV Patients 10 Clin UPIN Diagnosis Dx Dur Gscore Score 124 PV 13 2 1 124 PV 21 1 0 136 PV 11 2 1 183 PV 14 3 0 199 PV/MF 18 4 2 294 PV 8 2 1 326 PV 17 4 3 351 PV 16 2 0 355 PV 10 2 2 398 PV 6 3 1 470 PV 26 0 3 495 PV 6 2 0 564 PV 11 4 1 645 PV 11 2 1 914 PV 10 3 1 1045 PV 9 2 1 1073 PV 8 4 1 1092 PV 7 2 1 1125 PV 27 4 3 1191 PV 10 4 1 1267 PV 4 2 0 1308 PV 10 4 1 1370 PV 4 1 2 1418 PV 7 4 2 1428 PV 1 3 0 1428 PV 4 4 1 1433 PV 3 4 0 1438 PV 3 4 2 1439 PV 3 3 1 1459 PV 4 3 2 1529 PV 2.5 3 0 1542 PV 1 3 0 1542 PV 1 2 0 1552 PV 1 2 0 1552 PV 2 1 0 1574 PV 13 2 3 1574 PV 2 2 0 1578 PV 7 4 0 1585 PV 1.5 2 0 1591 PV 3 3 1 1599 PV 8 1 0 1635 PV 1.5 2 0 1127 PV 11 3 0 Average 2.651163 0.906977 Median 3 1 Mann-Whitney U Statistic p < 0.001 p < 0.001 compared to PV Aggressive

TABLE 19 10 Gene Screening Data from Aggressive PV Patients 10 Clin UPIN Diagnosis Dx Dur Gscore Score 113 PV/MF 19 5 5 173 PV/MF 28 5 4 206 PV/MF/AML 18 6 6 249 PV 18 5 3 671 PV/MF 24 5 2 680 PV/MF 12 5 3 1113 PV/MF 7 5 5 1113 PV/MF 12 5 5 1235 PV 9 5 2 1253 PV 4 5 2 1463 PV/MF 39 5 3 1545 PV 11 5 1 1596 PV/MF 13 5 1 1639 PV 4 6 3 999 PV/MF 11 6 3 682 PV/MF/SM 20 5 3 Mean 5.1875 3.1875 Median 5 3 Mann-Whitney U Statistic p < 0.001 p < 0.001 compared to PV Indolent 

1. A method for predicting the likelihood of an indolent form of Polycythemia Vera (PV) transforming to an aggressive form of PV in a subject, the method comprising: (a) measuring the gene products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 in a biological sample comprising blood cells obtained from the subject; (b) making the following comparisons of the gene product levels measured in (a) and recording a score of 1 for a true result and a score of 0 for a false result: PCNA>IFI30; TSN>CTSA; SMC4>CDKN1A; PCNA>CTTN; SON>CTTN; TIA1>MYL9; (c) adding the scores together to obtain an added score and calculating a ratio of the added score/6 to calculate a total score; and (d) predicting based on the total score calculated in (c) the likelihood of the indolent form of PV in the subject to transform to an aggressive form of PV.
 2. The method of claim 1, wherein a total score of 5/6 or 6/6 predicts that the indolent form of PV in a subject is likely to transform to an aggressive form of PV in the subject.
 3. The method of claim 1, wherein a total score of less than 5/6 predicts that the indolent form of PV in a subject is not likely to transform to an aggressive form of PV in the subject.
 4. The method of claim 1, wherein the blood cells are white blood cells.
 5. The method of claim 1, wherein the blood cells are CD34+ cells.
 6. The method of claim 1, wherein the subject is mammalian.
 7. The method of claim 6, wherein the subject is human.
 8. The method of claim 1, wherein the expression products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 are measured by determining mRNA expression levels.
 9. The method of claim 8, wherein the mRNA expression levels are measured by using reverse transcription PCR (RT-PCR).
 10. The method of claim 9, wherein the reverse transcription PCR (RT-PCR) is followed by real-time PCR (Q-PCR).
 11. The method of claim 1, wherein the expression products of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 are measured by determining protein expression levels.
 12. The method of claim 1, wherein the biological sample comprises peripheral blood or bone marrow.
 13. The method of claim 1, wherein the indolent form of PV is characterized by at least one of symptom selected from the group consisting of increased production of red cells, increased production of white cells, increased production of platelets, itching, gouty arthritis peptic ulcer disease, enlarged liver or spleen, elevated hemoglobin levels, and low erythropoietin levels in the subject.
 14. The method of claim 1, wherein the aggressive form of PV is characterized by at least one symptom selected from the group consisting of thrombosis, heart attack, stroke, Budd-Chiari syndrome, myelofibrosis and acute leukemia (AML) in the subject.
 15. The method of claim 1, wherein the method displays a sensitivity of at least 80% and a specificity of at least 90%.
 16. The method of claim 1, further comprising informing the subject or a treating physician of the likelihood of the indolent form of Polycythemia Vera (PV) transforming to an aggressive form of PV in the subject.
 17. The method of claim 1, wherein the method is used to determine if a subject should undergo further therapy for PV.
 18. The method of claim 17, further comprising treating the patient with further therapy for PV.
 19. The method of claim 18, wherein the therapy is selected from the group consisting of bone marrow transplantation, pegylated interferon, chemotherapy, and ruxolitinib.
 20. A diagnostic kit for determining whether an indolent form of PV in a subject is likely to transform to an aggressive form of PV, the kit comprising a means for measuring the gene product levels of PCNA, IFI30, TSN, CTSA, SMC4, CDKN1A, CTTN, SON, TIA1, and MYL9 and a set of instructions comprising an algorithm for predicting if the indolent form of PV in the subject is likely to transform to an aggressive form of PV. 